Abstract
The POU (Pit-Oct-Unc) protein family is an evolutionary ancient group of transcription factors (TFs) that bind specific DNA sequences to direct gene expression programs. The fundamental importance of POU TFs to orchestrate embryonic development and to direct cellular fate decisions is well established, but the molecular basis for this activity is insufficiently understood. POU TFs possess a bipartite ‘two-in-one’ DNA binding domain consisting of two independently folding structural units connected by a poorly conserved and flexible linker. Therefore, they represent a paradigmatic example to study the molecular basis for the functional versatility of TFs. Their modular architecture endows POU TFs with the capacity to accommodate alternative composite DNA sequences by adopting different quaternary structures. Moreover, associations with partner proteins crucially influence the selection of their DNA binding sites. The plentitude of DNA binding modes confers the ability to POU TFs to regulate distinct genes in the context of different cellular environments. Likewise, different binding modes of POU proteins to DNA could trigger alternative regulatory responses in the context of different genomic locations of the same cell. Prominent POU TFs such as Oct4, Brn2, Oct6 and Brn4 are not only essential regulators of development but have also been successfully employed to reprogram somatic cells to pluripotency and neural lineages. Here we review biochemical, structural, genomic and cellular reprogramming studies to examine how the ability of POU TFs to select regulatory DNA, alone or with partner factors, is tied to their capacity to epigenetically remodel chromatin and drive specific regulatory programs that give cells their identities.
Similar content being viewed by others
References
Parslow TG, Blair DL, Murphy WJ, Granner DK (1984) Structure of the 5′ ends of immunoglobulin genes: a novel conserved sequence. Proc Natl Acad Sci USA 81(9):2650–2654
Carbon P, Murgo S, Ebel JP, Krol A, Tebb G, Mattaj LW (1987) A common octamer motif binding protein is involved in the transcription of U6 snRNA by RNA polymerase III and U2 snRNA by RNA polymerase II. Cell 51(1):71–79
LaBella F, Sive HL, Roeder RG, Heintz N (1988) Cell-cycle regulation of a human histone H2b gene is mediated by the H2b subtype-specific consensus element. Genes Dev 2(1):32–39
Pruijn GJ, van Driel W, van der Vliet PC (1986) Nuclear factor III, a novel sequence-specific DNA-binding protein from HeLa cells stimulating adenovirus DNA replication. Nature 322(6080):656–659. https://doi.org/10.1038/322656a0
Sturm R, Baumruker T, Franza BR Jr, Herr W (1987) A 100-kD HeLa cell octamer binding protein (OBP100) interacts differently with two separate octamer-related sequences within the SV40 enhancer. Genes Dev 1(10):1147–1160
Staudt LM, Singh H, Sen R, Wirth T, Sharp PA, Baltimore D (1986) A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes. Nature 323(6089):640–643. https://doi.org/10.1038/323640a0
Fletcher C, Heintz N, Roeder RG (1987) Purification and characterization of OTF-1, a transcription factor regulating cell cycle expression of a human histone H2b gene. Cell 51(5):773–781
Hanke JH, Landolfi NF, Tucker PW, Capra JD (1988) Identification of murine nuclear proteins that bind to the conserved octamer sequence of the immunoglobulin promoter region. Proc Natl Acad Sci USA 85(10):3560–3564
Scheidereit C, Heguy A, Roeder RG (1987) Identification and purification of a human lymphoid-specific octamer-binding protein (OTF-2) that activates transcription of an immunoglobulin promoter in vitro. Cell 51(5):783–793
O’Neill EA, Kelly TJ (1988) Purification and characterization of nuclear factor III (origin recognition protein C), a sequence-specific DNA binding protein required for efficient initiation of adenovirus DNA replication. J Biol Chem 263(2):931–937
Clerc RG, Corcoran LM, LeBowitz JH, Baltimore D, Sharp PA (1988) The B-cell-specific Oct-2 protein contains POU box- and homeo box-type domains. Genes Dev 2(12A):1570–1581
Ko HS, Fast P, McBride W, Staudt LM (1988) A human protein specific for the immunoglobulin octamer DNA motif contains a functional homeobox domain. Cell 55(1):135–144
Muller MM, Ruppert S, Schaffner W, Matthias P (1988) A cloned octamer transcription factor stimulates transcription from lymphoid-specific promoters in non-B cells. Nature 336(6199):544–551. https://doi.org/10.1038/336544a0
Scheidereit C, Cromlish JA, Gerster T, Kawakami K, Balmaceda CG, Currie RA, Roeder RG (1988) A human lymphoid-specific transcription factor that activates immunoglobulin genes is a homoeobox protein. Nature 336(6199):551–557. https://doi.org/10.1038/336551a0
Bodner M, Castrillo JL, Theill LE, Deerinck T, Ellisman M, Karin M (1988) The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein. Cell 55(3):505–518
Ingraham HA, Chen RP, Mangalam HJ, Elsholtz HP, Flynn SE, Lin CR, Simmons DM, Swanson L, Rosenfeld MG (1988) A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype. Cell 55(3):519–529
Finney M, Ruvkun G, Horvitz HR (1988) The C. elegans cell lineage and differentiation gene unc-86 encodes a protein with a homeodomain and extended similarity to transcription factors. Cell 55(5):757–769
Herr W, Sturm RA, Clerc RG, Corcoran LM, Baltimore D, Sharp PA, Ingraham HA, Rosenfeld MG, Finney M, Ruvkun G et al (1988) The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products. Genes Dev 2(12A):1513–1516
McGinnis W, Garber RL, Wirz J, Kuroiwa A, Gehring WJ (1984) A homologous protein-coding sequence in Drosophila homeotic genes and its conservation in other metazoans. Cell 37(2):403–408
Scott MP, Weiner AJ (1984) Structural relationships among genes that control development: sequence homology between the Antennapedia, Ultrabithorax, and fushi tarazu loci of Drosophila. Proc Natl Acad Sci USA 81(13):4115–4119
Robertson M (1988) Homoeo boxes, POU proteins and the limits to promiscuity. Nature 336(6199):522–524. https://doi.org/10.1038/336522a0
Herr W, Cleary MA (1995) The POU domain: versatility in transcriptional regulation by a flexible two-in-one DNA-binding domain. Genes Dev 9(14):1679–1693
Jerabek S, Merino F, Scholer HR, Cojocaru V (2014) OCT4: dynamic DNA binding pioneers stem cell pluripotency. Biochim Biophys Acta 1839(3):138–154. https://doi.org/10.1016/j.bbagrm.2013.10.001
Phillips K, Luisi B (2000) The virtuoso of versatility: POU proteins that flex to fit. J Mol Biol 302(5):1023–1039. https://doi.org/10.1006/jmbi.2000.4107
Remenyi A, Tomilin A, Scholer HR, Wilmanns M (2002) Differential activity by DNA-induced quarternary structures of POU transcription factors. Biochem Pharmacol 64(5–6):979–984
Ryan AK, Rosenfeld MG (1997) POU domain family values: flexibility, partnerships, and developmental codes. Genes Dev 11(10):1207–1225
Tantin D (2013) Oct transcription factors in development and stem cells: insights and mechanisms. Development 140(14):2857–2866. https://doi.org/10.1242/dev.095927
Verrijzer CP, Van der Vliet PC (1993) POU domain transcription factors. Biochim Biophys Acta 1173(1):1–21
Wegner M, Drolet DW, Rosenfeld MG (1993) POU-domain proteins: structure and function of developmental regulators. Curr Opin Cell Biol 5(3):488–498
Gold DA, Gates RD, Jacobs DK (2014) The early expansion and evolutionary dynamics of POU class genes. Mol Biol Evol 31(12):3136–3147. https://doi.org/10.1093/molbev/msu243
Rosenfeld MG (1991) POU-domain transcription factors: pou-er-ful developmental regulators. Genes Dev 5(6):897–907
Holland PW, Booth HA, Bruford EA (2007) Classification and nomenclature of all human homeobox genes. BMC Biol 5:47. https://doi.org/10.1186/1741-7007-5-47
Scholer HR (1991) Octamania: the POU factors in murine development. Trends Genet 7(10):323–329
Hutchins AP, Yang Z, Li Y, He F, Fu X, Wang X, Li D, Liu K, He J, Wang Y, Chen J, Esteban MA, Pei D (2017) Models of global gene expression define major domains of cell type and tissue identity. Nucleic Acids Res 45(5):2354–2367. https://doi.org/10.1093/nar/gkx054
Sturm RA, Das G, Herr W (1988) The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. Genes Dev 2(12A):1582–1599
Landolfi NF, Capra JD, Tucker PW (1986) Interaction of cell-type-specific nuclear proteins with immunoglobulin VH promoter region sequences. Nature 323(6088):548–551. https://doi.org/10.1038/323548a0
Staudt LM, Clerc RG, Singh H, LeBowitz JH, Sharp PA, Baltimore D (1988) Cloning of a lymphoid-specific cDNA encoding a protein binding the regulatory octamer DNA motif. Science 241(4865):577–580
Andersen B, Weinberg WC, Rennekampff O, McEvilly RJ, Bermingham JR Jr, Hooshmand F, Vasilyev V, Hansbrough JF, Pittelkow MR, Yuspa SH, Rosenfeld MG (1997) Functions of the POU domain genes Skn-1a/i and Tst-1/Oct-6/SCIP in epidermal differentiation. Genes Dev 11(14):1873–1884
Matsumoto I, Ohmoto M, Narukawa M, Yoshihara Y, Abe K (2011) Skn-1a (Pou2f3) specifies taste receptor cell lineage. Nat Neurosci 14(6):685–687. https://doi.org/10.1038/nn.2820
Andersen B, Schonemann MD, Pearse RV 2nd, Jenne K, Sugarman J, Rosenfeld MG (1993) Brn-5 is a divergent POU domain factor highly expressed in layer IV of the neocortex. J Biol Chem 268(31):23390–23398
He X, Treacy MN, Simmons DM, Ingraham HA, Swanson LW, Rosenfeld MG (1989) Expression of a large family of POU-domain regulatory genes in mammalian brain development. Nature 340(6228):35–41. https://doi.org/10.1038/340035a0
Mathis JM, Simmons DM, He X, Swanson LW, Rosenfeld MG (1992) Brain 4: a novel mammalian POU domain transcription factor exhibiting restricted brain-specific expression. EMBO J 11(7):2551–2561
Wey E, Lyons GE, Schafer BW (1994) A human POU domain gene, mPOU, is expressed in developing brain and specific adult tissues. Eur J Biochem 220(3):753–762
Monuki ES, Weinmaster G, Kuhn R, Lemke G (1989) SCIP: a glial POU domain gene regulated by cyclic AMP. Neuron 3(6):783–793
Suzuki N, Rohdewohld H, Neuman T, Gruss P, Scholer HR (1990) Oct-6: a POU transcription factor expressed in embryonal stem cells and in the developing brain. EMBO J 9(11):3723–3732
Nakai S, Kawano H, Yudate T, Nishi M, Kuno J, Nagata A, Jishage K, Hamada H, Fujii H, Kawamura K et al (1995) The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse. Genes Dev 9(24):3109–3121
Schonemann MD, Ryan AK, McEvilly RJ, O’Connell SM, Arias CA, Kalla KA, Li P, Sawchenko PE, Rosenfeld MG (1995) Development and survival of the endocrine hypothalamus and posterior pituitary gland requires the neuronal POU domain factor Brn-2. Genes Dev 9(24):3122–3135
Scholer HR, Hatzopoulos AK, Balling R, Suzuki N, Gruss P (1989) A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor. EMBO J 8(9):2543–2550
Schreiber E, Harshman K, Kemler I, Malipiero U, Schaffner W, Fontana A (1990) Astrocytes and glioblastoma cells express novel octamer-DNA binding proteins distinct from the ubiquitous Oct-1 and B cell type Oct-2 proteins. Nucleic Acids Res 18(18):5495–5503
Gerrero MR, McEvilly RJ, Turner E, Lin CR, O’Connell S, Jenne KJ, Hobbs MV, Rosenfeld MG (1993) Brn-3.0: a POU-domain protein expressed in the sensory, immune, and endocrine systems that functions on elements distinct from known octamer motifs. Proc Natl Acad Sci USA 90(22):10841–10845
Lillycrop KA, Budrahan VS, Lakin ND, Terrenghi G, Wood JN, Polak JM, Latchman DS (1992) A novel POU family transcription factor is closely related to Brn-3 but has a distinct expression pattern in neuronal cells. Nucleic Acids Res 20(19):5093–5096
Turner EE, Jenne KJ, Rosenfeld MG (1994) Brn-3.2: a Brn-3-related transcription factor with distinctive central nervous system expression and regulation by retinoic acid. Neuron 12(1):205–218
Xiang M, Zhou L, Peng YW, Eddy RL, Shows TB, Nathans J (1993) Brn-3b: a POU domain gene expressed in a subset of retinal ganglion cells. Neuron 11(4):689–701
Ninkina NN, Stevens GE, Wood JN, Richardson WD (1993) A novel Brn3-like POU transcription factor expressed in subsets of rat sensory and spinal cord neurons. Nucleic Acids Res 21(14):3175–3182
Zhou H, Yoshioka T, Nathans J (1996) Retina-derived POU-domain factor-1: a complex POU-domain gene implicated in the development of retinal ganglion and amacrine cells. J Neurosci 16(7):2261–2274
Lenardo MJ, Staudt L, Robbins P, Kuang A, Mulligan RC, Baltimore D (1989) Repression of the IgH enhancer in teratocarcinoma cells associated with a novel octamer factor. Science 243(4890):544–546
Okamoto KOH, Okuda A, Sakai M, Muramatsu M, Hamada H (1990) A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells. Cell 60(3):461–472. https://doi.org/10.1016/0092-8674(90)90597-8
Scholer HR, Ruppert S, Suzuki N, Chowdhury K, Gruss P (1990) New type of POU domain in germ line-specific protein Oct-4. Nature 344(6265):435–439. https://doi.org/10.1038/344435a0
Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Scholer H, Smith A (1998) Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95(3):379–391
Niwa H, Miyazaki J, Smith AG (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24(4):372–376. https://doi.org/10.1038/74199
Yuan H, Corbi N, Basilico C, Dailey L (1995) Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3. Genes Dev 9(21):2635–2645
Takeda J, Seino S, Bell GI (1992) Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues. Nucleic Acids Res 20(17):4613–4620
Mizuno N, Kosaka M (2008) Novel variants of Oct-3/4 gene expressed in mouse somatic cells. J Biol Chem 283(45):30997–31004. https://doi.org/10.1074/jbc.M802992200
Lee J, Kim HK, Rho JY, Han YM, Kim J (2006) The human OCT-4 isoforms differ in their ability to confer self-renewal. J Biol Chem 281(44):33554–33565. https://doi.org/10.1074/jbc.M603937200
Atlasi Y, Mowla SJ, Ziaee SA, Gokhale PJ, Andrews PW (2008) OCT4 spliced variants are differentially expressed in human pluripotent and nonpluripotent cells. Stem Cells 26(12):3068–3074. https://doi.org/10.1634/stemcells.2008-0530
Andersen B, Pearse RV 2nd, Schlegel PN, Cichon Z, Schonemann MD, Bardin CW, Rosenfeld MG (1993) Sperm 1: a POU-domain gene transiently expressed immediately before meiosis I in the male germ cell. Proc Natl Acad Sci USA 90(23):11084–11088
Pearse RV 2nd, Drolet DW, Kalla KA, Hooshmand F, Bermingham JR Jr, Rosenfeld MG (1997) Reduced fertility in mice deficient for the POU protein sperm-1. Proc Natl Acad Sci USA 94(14):7555–7560
Frankenberg SR, Frank D, Harland R, Johnson AD, Nichols J, Niwa H, Scholer HR, Tanaka E, Wylie C, Brickman JM (2014) The POU-er of gene nomenclature. Development 141(15):2921–2923. https://doi.org/10.1242/dev.108407
Takeda H, Matsuzaki T, Oki T, Miyagawa T, Amanuma H (1994) A novel POU domain gene, zebrafish pou2: expression and roles of two alternatively spliced twin products in early development. Genes Dev 8(1):45–59
Weintraub H, Tapscott SJ, Davis RL, Thayer MJ, Adam MA, Lassar AB, Miller AD (1989) Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc Natl Acad Sci USA 86(14):5434–5438
Xie H, Ye M, Feng R, Graf T (2004) Stepwise reprogramming of B cells into macrophages. Cell 117(5):663–676
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872. https://doi.org/10.1016/j.cell.2007.11.019
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676. https://doi.org/10.1016/j.cell.2006.07.024
Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920. https://doi.org/10.1126/science.1151526
Bar-Nur O, Verheul C, Sommer AG, Brumbaugh J, Schwarz BA, Lipchina I, Huebner AJ, Mostoslavsky G, Hochedlinger K (2015) Lineage conversion induced by pluripotency factors involves transient passage through an iPSC stage. Nat Biotechnol 33(7):761–768. https://doi.org/10.1038/nbt.3247
Han DW, Tapia N, Hermann A, Hemmer K, Hoing S, Arauzo-Bravo MJ, Zaehres H, Wu G, Frank S, Moritz S, Greber B, Yang JH, Lee HT, Schwamborn JC, Storch A, Scholer HR (2012) Direct reprogramming of fibroblasts into neural stem cells by defined factors. Cell Stem Cell 10(4):465–472. https://doi.org/10.1016/j.stem.2012.02.021
Kim J, Efe JA, Zhu S, Talantova M, Yuan X, Wang S, Lipton SA, Zhang K, Ding S (2011) Direct reprogramming of mouse fibroblasts to neural progenitors. Proc Natl Acad Sci USA 108(19):7838–7843. https://doi.org/10.1073/pnas.1103113108
Lujan E, Chanda S, Ahlenius H, Sudhof TC, Wernig M (2012) Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells. Proc Natl Acad Sci USA 109(7):2527–2532. https://doi.org/10.1073/pnas.1121003109
Thier M, Worsdorfer P, Lakes YB, Gorris R, Herms S, Opitz T, Seiferling D, Quandel T, Hoffmann P, Nothen MM, Brustle O, Edenhofer F (2012) Direct conversion of fibroblasts into stably expandable neural stem cells. Cell Stem Cell 10(4):473–479. https://doi.org/10.1016/j.stem.2012.03.003
Zhu S, Ambasudhan R, Sun W, Kim HJ, Talantova M, Wang X, Zhang M, Zhang Y, Laurent T, Parker J, Kim HS, Zaremba JD, Saleem S, Sanz-Blasco S, Masliah E, McKercher SR, Cho YS, Lipton SA, Kim J, Ding S (2014) Small molecules enable OCT4-mediated direct reprogramming into expandable human neural stem cells. Cell Res 24(1):126–129. https://doi.org/10.1038/cr.2013.156
Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S, Lipton SA, Ding S (2011) Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell 9(2):113–118. https://doi.org/10.1016/j.stem.2011.07.002
Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, Citri A, Sebastiano V, Marro S, Sudhof TC, Wernig M (2011) Induction of human neuronal cells by defined transcription factors. Nature 476(7359):220–223. https://doi.org/10.1038/nature10202
Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M (2010) Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463(7284):1035–1041. https://doi.org/10.1038/nature08797
Wang H, Cao N, Spencer CI, Nie B, Ma T, Xu T, Zhang Y, Wang X, Srivastava D, Ding S (2014) Small molecules enable cardiac reprogramming of mouse fibroblasts with a single factor, Oct4. Cell Rep 6(5):951–960. https://doi.org/10.1016/j.celrep.2014.01.038
Wapinski OL, Vierbuchen T, Qu K, Lee QY, Chanda S, Fuentes DR, Giresi PG, Ng YH, Marro S, Neff NF, Drechsel D, Martynoga B, Castro DS, Webb AE, Sudhof TC, Brunet A, Guillemot F, Chang HY, Wernig M (2013) Hierarchical mechanisms for direct reprogramming of fibroblasts to neurons. Cell 155(3):621–635. https://doi.org/10.1016/j.cell.2013.09.028
Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S (2008) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26(1):101–106. https://doi.org/10.1038/nbt1374
Jerabek S, Ng CK, Wu G, Arauzo-Bravo MJ, Kim KP, Esch D, Malik V, Chen Y, Velychko S, MacCarthy CM, Yang X, Cojocaru V, Scholer HR, Jauch R (2017) Changing POU dimerization preferences converts Oct6 into a pluripotency inducer. EMBO Rep 18(2):319–333. https://doi.org/10.15252/embr.201642958
Kim JB, Greber B, Arauzo-Bravo MJ, Meyer J, Park KI, Zaehres H, Scholer HR (2009) Direct reprogramming of human neural stem cells by OCT4. Nature 461(7264):649–653. https://doi.org/10.1038/nature08436
Kim JB, Sebastiano V, Wu G, Arauzo-Bravo MJ, Sasse P, Gentile L, Ko K, Ruau D, Ehrich M, van den Boom D, Meyer J, Hubner K, Bernemann C, Ortmeier C, Zenke M, Fleischmann BK, Zaehres H, Scholer HR (2009) Oct4-induced pluripotency in adult neural stem cells. Cell 136(3):411–419. https://doi.org/10.1016/j.cell.2009.01.023
Ebert AD, Yu J, Rose FF Jr, Mattis VB, Lorson CL, Thomson JA, Svendsen CN (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457(7227):277–280. https://doi.org/10.1038/nature07677
Lee G, Papapetrou EP, Kim H, Chambers SM, Tomishima MJ, Fasano CA, Ganat YM, Menon J, Shimizu F, Viale A, Tabar V, Sadelain M, Studer L (2009) Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 461(7262):402–406. https://doi.org/10.1038/nature08320
Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, Eggan K (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321(5893):1218–1221. https://doi.org/10.1126/science.1158799
Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, Isacson O, Jaenisch R (2009) Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136(5):964–977. https://doi.org/10.1016/j.cell.2009.02.013
Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ (2008) Disease-specific induced pluripotent stem cells. Cell 134(5):877–886. https://doi.org/10.1016/j.cell.2008.07.041
Zhou T, Benda C, Dunzinger S, Huang Y, Ho JC, Yang J, Wang Y, Zhang Y, Zhuang Q, Li Y, Bao X, Tse HF, Grillari J, Grillari-Voglauer R, Pei D, Esteban MA (2012) Generation of human induced pluripotent stem cells from urine samples. Nat Protoc 7(12):2080–2089. https://doi.org/10.1038/nprot.2012.115
Lujan E, Wernig M (2012) The many roads to Rome: induction of neural precursor cells from fibroblasts. Curr Opin Genet Dev 22(5):517–522. https://doi.org/10.1016/j.gde.2012.07.002
Lin C, Yu C, Ding S (2013) Toward directed reprogramming through exogenous factors. Curr Opin Genet Dev 23(5):519–525. https://doi.org/10.1016/j.gde.2013.06.002
Yu C, Liu K, Tang S, Ding S (2014) Chemical approaches to cell reprogramming. Curr Opin Genet Dev 28:50–56. https://doi.org/10.1016/j.gde.2014.09.006
Li K, Zhu S, Russ HA, Xu S, Xu T, Zhang Y, Ma T, Hebrok M, Ding S (2014) Small molecules facilitate the reprogramming of mouse fibroblasts into pancreatic lineages. Cell Stem Cell 14(2):228–236. https://doi.org/10.1016/j.stem.2014.01.006
Zhu S, Rezvani M, Harbell J, Mattis AN, Wolfe AR, Benet LZ, Willenbring H, Ding S (2014) Mouse liver repopulation with hepatocytes generated from human fibroblasts. Nature 508(7494):93–97. https://doi.org/10.1038/nature13020
Efe JA, Hilcove S, Kim J, Zhou H, Ouyang K, Wang G, Chen J, Ding S (2011) Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy. Nat Cell Biol 13(3):215–222. https://doi.org/10.1038/ncb2164
Li J, Huang NF, Zou J, Laurent TJ, Lee JC, Okogbaa J, Cooke JP, Ding S (2013) Conversion of human fibroblasts to functional endothelial cells by defined factors. Arterioscler Thromb Vasc Biol 33(6):1366–1375. https://doi.org/10.1161/ATVBAHA.112.301167
Szabo E, Rampalli S, Risueno RM, Schnerch A, Mitchell R, Fiebig-Comyn A, Levadoux-Martin M, Bhatia M (2010) Direct conversion of human fibroblasts to multilineage blood progenitors. Nature 468(7323):521–526. https://doi.org/10.1038/nature09591
Maza I, Caspi I, Zviran A, Chomsky E, Rais Y, Viukov S, Geula S, Buenrostro JD, Weinberger L, Krupalnik V, Hanna S, Zerbib M, Dutton JR, Greenleaf WJ, Massarwa R, Novershtern N, Hanna JH (2015) Transient acquisition of pluripotency during somatic cell transdifferentiation with iPSC reprogramming factors. Nat Biotechnol 33(7):769–774. https://doi.org/10.1038/nbt.3270
Marro S, Pang ZP, Yang N, Tsai MC, Qu K, Chang HY, Sudhof TC, Wernig M (2011) Direct lineage conversion of terminally differentiated hepatocytes to functional neurons. Cell Stem Cell 9(4):374–382. https://doi.org/10.1016/j.stem.2011.09.002
Qiang L, Fujita R, Yamashita T, Angulo S, Rhinn H, Rhee D, Doege C, Chau L, Aubry L, Vanti WB, Moreno H, Abeliovich A (2011) Directed conversion of Alzheimer’s disease patient skin fibroblasts into functional neurons. Cell 146(3):359–371. https://doi.org/10.1016/j.cell.2011.07.007
Yoo AS, Sun AX, Li L, Shcheglovitov A, Portmann T, Li Y, Lee-Messer C, Dolmetsch RE, Tsien RW, Crabtree GR (2011) MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 476(7359):228–231. https://doi.org/10.1038/nature10323
Pfisterer U, Kirkeby A, Torper O, Wood J, Nelander J, Dufour A, Bjorklund A, Lindvall O, Jakobsson J, Parmar M (2011) Direct conversion of human fibroblasts to dopaminergic neurons. Proc Natl Acad Sci USA 108(25):10343–10348. https://doi.org/10.1073/pnas.1105135108
Verrijzer CP, Alkema MJ, van Weperen WW, Van Leeuwen HC, Strating MJ, van der Vliet PC (1992) The DNA binding specificity of the bipartite POU domain and its subdomains. EMBO J 11(13):4993–5003
Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, Cheng JX, Murre C, Singh H, Glass CK (2010) Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell 38(4):576–589. https://doi.org/10.1016/j.molcel.2010.05.004
Assa-Munt N, Mortishire-Smith RJ, Aurora R, Herr W, Wright PE (1993) The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain. Cell 73(1):193–205
Dekker N, Cox M, Boelens R, Verrijzer CP, van der Vliet PC, Kaptein R (1993) Solution structure of the POU-specific DNA-binding domain of Oct-1. Nature 362(6423):852–855. https://doi.org/10.1038/362852a0
Cox M, van Tilborg PJ, de Laat W, Boelens R, van Leeuwen HC, van der Vliet PC, Kaptein R (1995) Solution structure of the Oct-1 POU homeodomain determined by NMR and restrained molecular dynamics. J Biomol NMR 6(1):23–32
Morita EH, Shirakawa M, Hayashi F, Imagawa M, Kyogoku Y (1995) Structure of the Oct-3 POU-homeodomain in solution, as determined by triple resonance heteronuclear multidimensional NMR spectroscopy. Protein Sci 4(4):729–739. https://doi.org/10.1002/pro.5560040412
Klemm JD, Rould MA, Aurora R, Herr W, Pabo CO (1994) Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules. Cell 77(1):21–32
Ferraris L, Stewart AP, Kang J, DeSimone AM, Gemberling M, Tantin D, Fairbrother WG (2011) Combinatorial binding of transcription factors in the pluripotency control regions of the genome. Genome Res 21(7):1055–1064. https://doi.org/10.1101/gr.115824.110
Baburajendran N, Jauch R, Tan CY, Narasimhan K, Kolatkar PR (2011) Structural basis for the cooperative DNA recognition by Smad4 MH1 dimers. Nucleic Acids Res 39(18):8213–8222. https://doi.org/10.1093/nar/gkr500
Kim S, Brostromer E, Xing D, Jin J, Chong S, Ge H, Wang S, Gu C, Yang L, Gao YQ, Su XD, Sun Y, Xie XS (2013) Probing allostery through DNA. Science 339(6121):816–819. https://doi.org/10.1126/science.1229223
Narasimhan K, Pillay S, Huang YH, Jayabal S, Udayasuryan B, Veerapandian V, Kolatkar P, Cojocaru V, Pervushin K, Jauch R (2015) DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors. Nucleic Acids Res 43(3):1513–1528. https://doi.org/10.1093/nar/gku1390
Merino F, Bouvier B, Cojocaru V (2015) Cooperative DNA recognition modulated by an interplay between protein–protein interactions and DNA-mediated allostery. PLoS Comput Biol 11(6):e1004287. https://doi.org/10.1371/journal.pcbi.1004287
Badis G, Berger MF, Philippakis AA, Talukder S, Gehrke AR, Jaeger SA, Chan ET, Metzler G, Vedenko A, Chen X, Kuznetsov H, Wang CF, Coburn D, Newburger DE, Morris Q, Hughes TR, Bulyk ML (2009) Diversity and complexity in DNA recognition by transcription factors. Science 324(5935):1720–1723. https://doi.org/10.1126/science.1162327
Weirauch MT, Yang A, Albu M, Cote AG, Montenegro-Montero A, Drewe P, Najafabadi HS, Lambert SA, Mann I, Cook K, Zheng H, Goity A, van Bakel H, Lozano JC, Galli M, Lewsey MG, Huang E, Mukherjee T, Chen X, Reece-Hoyes JS, Govindarajan S, Shaulsky G, Walhout AJM, Bouget FY, Ratsch G, Larrondo LF, Ecker JR, Hughes TR (2014) Determination and inference of eukaryotic transcription factor sequence specificity. Cell 158(6):1431–1443. https://doi.org/10.1016/j.cell.2014.08.009
Takayama Y, Clore GM (2011) Intra- and intermolecular translocation of the bi-domain transcription factor Oct1 characterized by liquid crystal and paramagnetic NMR. Proc Natl Acad Sci USA 108(22):E169–176. https://doi.org/10.1073/pnas.1100050108
Kemler I, Schreiber E, Muller MM, Matthias P, Schaffner W (1989) Octamer transcription factors bind to two different sequence motifs of the immunoglobulin heavy chain promoter. EMBO J 8(7):2001–2008
LeBowitz JH, Clerc RG, Brenowitz M, Sharp PA (1989) The Oct-2 protein binds cooperatively to adjacent octamer sites. Genes Dev 3(10):1625–1638
Poellinger L, Roeder RG (1989) Octamer transcription factors 1 and 2 each bind to two different functional elements in the immunoglobulin heavy-chain promoter. Mol Cell Biol 9(2):747–756
Rhee JM, Gruber CA, Brodie TB, Trieu M, Turner EE (1998) Highly cooperative homodimerization is a conserved property of neural POU proteins. J Biol Chem 273(51):34196–34205
Jacobson EM, Li P, Leon-del-Rio A, Rosenfeld MG, Aggarwal AK (1997) Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility. Genes Dev 11(2):198–212
Tomilin A, Remenyi A, Lins K, Bak H, Leidel S, Vriend G, Wilmanns M, Scholer HR (2000) Synergism with the coactivator OBF-1 (OCA-B, BOB-1) is mediated by a specific POU dimer configuration. Cell 103(6):853–864
Remenyi A, Tomilin A, Pohl E, Lins K, Philippsen A, Reinbold R, Scholer HR, Wilmanns M (2001) Differential dimer activities of the transcription factor Oct-1 by DNA-induced interface swapping. Mol Cell 8(3):569–580
Jauch R, Choo SH, Ng CK, Kolatkar PR (2011) Crystal structure of the dimeric Oct6 (POU3f1) POU domain bound to palindromic MORE DNA. Proteins 79(2):674–677. https://doi.org/10.1002/prot.22916
Scully KM, Jacobson EM, Jepsen K, Lunyak V, Viadiu H, Carriere C, Rose DW, Hooshmand F, Aggarwal AK, Rosenfeld MG (2000) Allosteric effects of Pit-1 DNA sites on long-term repression in cell type specification. Science 290(5494):1127–1131
Botquin V, Hess H, Fuhrmann G, Anastassiadis C, Gross MK, Vriend G, Scholer HR (1998) New POU dimer configuration mediates antagonistic control of an osteopontin preimplantation enhancer by Oct-4 and Sox-2. Genes Dev 12(13):2073–2090
Skowronska-Krawczyk D, Ma Q, Schwartz M, Scully K, Li W, Liu Z, Taylor H, Tollkuhn J, Ohgi KA, Notani D, Kohwi Y, Kohwi-Shigematsu T, Rosenfeld MG (2014) Required enhancer-matrin-3 network interactions for a homeodomain transcription program. Nature 514(7521):257–261. https://doi.org/10.1038/nature13573
Mistri TK, Devasia AG, Chu LT, Ng WP, Halbritter F, Colby D, Martynoga B, Tomlinson SR, Chambers I, Robson P, Wohland T (2015) Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cells. EMBO Rep 16(9):1177–1191. https://doi.org/10.15252/embr.201540467
Sharov AA, Ko MS (2009) Exhaustive search for over-represented DNA sequence motifs with CisFinder. DNA Res 16(5):261–273. https://doi.org/10.1093/dnares/dsp014
Lins K, Remenyi A, Tomilin A, Massa S, Wilmanns M, Matthias P, Scholer HR (2003) OBF1 enhances transcriptional potential of Oct1. EMBO J 22(9):2188–2198. https://doi.org/10.1093/emboj/cdg199
BabuRajendran N, Palasingam P, Narasimhan K, Sun W, Prabhakar S, Jauch R, Kolatkar PR (2010) Structure of Smad1 MH1/DNA complex reveals distinctive rearrangements of BMP and TGF-beta effectors. Nucleic Acids Res 38(10):3477–3488. https://doi.org/10.1093/nar/gkq046
Jolma A, Yan J, Whitington T, Toivonen J, Nitta KR, Rastas P, Morgunova E, Enge M, Taipale M, Wei G, Palin K, Vaquerizas JM, Vincentelli R, Luscombe NM, Hughes TR, Lemaire P, Ukkonen E, Kivioja T, Taipale J (2013) DNA-binding specificities of human transcription factors. Cell 152(1–2):327–339. https://doi.org/10.1016/j.cell.2012.12.009
Yin Y, Morgunova E, Jolma A, Kaasinen E, Sahu B, Khund-Sayeed S, Das PK, Kivioja T, Dave K, Zhong F, Nitta KR, Taipale M, Popov A, Ginno PA, Domcke S, Yan J, Schubeler D, Vinson C, Taipale J (2017) Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science 356(6337):eaaj2239. https://doi.org/10.1126/science.aaj2239
Palasingam P, Jauch R, Ng CK, Kolatkar PR (2009) The structure of Sox17 bound to DNA reveals a conserved bending topology but selective protein interaction platforms. J Mol Biol 388(3):619–630. https://doi.org/10.1016/j.jmb.2009.03.055
Remenyi A, Lins K, Nissen LJ, Reinbold R, Scholer HR, Wilmanns M (2003) Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers. Genes Dev 17(16):2048–2059. https://doi.org/10.1101/gad.269303
Jauch R, Ng CK, Narasimhan K, Kolatkar PR (2012) Crystal structure of the Sox4 HMG/DNA complex suggests a mechanism for the positional interdependence in DNA recognition. Biochem J 443(1):39–47. https://doi.org/10.1042/BJ20111768
Klaus M, Prokoph N, Girbig M, Wang X, Huang YH, Srivastava Y, Hou L, Narasimhan K, Kolatkar PR, Francois M, Jauch R (2016) Structure and decoy-mediated inhibition of the SOX18/Prox1–DNA interaction. Nucleic Acids Res 44(8):3922–3935. https://doi.org/10.1093/nar/gkw130
Werner MH, Huth JR, Gronenborn AM, Clore GM (1995) Molecular basis of human 46X, Y sex reversal revealed from the three-dimensional solution structure of the human SRY-DNA complex. Cell 81(5):705–714
Hou L, Srivastava Y, Jauch R (2016) Molecular basis for the genome engagement by Sox proteins. Semin Cell Dev Biol. https://doi.org/10.1016/j.semcdb.2016.08.005
Ambrosetti DC, Basilico C, Dailey L (1997) Synergistic activation of the fibroblast growth factor 4 enhancer by Sox2 and Oct-3 depends on protein–protein interactions facilitated by a specific spatial arrangement of factor binding sites. Mol Cell Biol 17(11):6321–6329
Dailey L, Yuan H, Basilico C (1994) Interaction between a novel F9-specific factor and octamer-binding proteins is required for cell-type-restricted activity of the fibroblast growth factor 4 enhancer. Mol Cell Biol 14(12):7758–7769
Nishimoto M, Fukushima A, Okuda A, Muramatsu M (1999) The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2. Mol Cell Biol 19(8):5453–5465
Nakatake Y, Fukui N, Iwamatsu Y, Masui S, Takahashi K, Yagi R, Yagi K, Miyazaki J, Matoba R, Ko MS, Niwa H (2006) Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Mol Cell Biol 26(20):7772–7782. https://doi.org/10.1128/MCB.00468-06
Tokuzawa Y, Kaiho E, Maruyama M, Takahashi K, Mitsui K, Maeda M, Niwa H, Yamanaka S (2003) Fbx15 is a novel target of Oct3/4 but is dispensable for embryonic stem cell self-renewal and mouse development. Mol Cell Biol 23(8):2699–2708
Rodda DJ, Chew JL, Lim LH, Loh YH, Wang B, Ng HH, Robson P (2005) Transcriptional regulation of nanog by OCT4 and SOX2. J Biol Chem 280(26):24731–24737. https://doi.org/10.1074/jbc.M502573200
Kuroda T, Tada M, Kubota H, Kimura H, Hatano SY, Suemori H, Nakatsuji N, Tada T (2005) Octamer and Sox elements are required for transcriptional cis regulation of Nanog gene expression. Mol Cell Biol 25(6):2475–2485. https://doi.org/10.1128/MCB.25.6.2475-2485.2005
Tomioka M, Nishimoto M, Miyagi S, Katayanagi T, Fukui N, Niwa H, Muramatsu M, Okuda A (2002) Identification of Sox-2 regulatory region which is under the control of Oct-3/4-Sox-2 complex. Nucleic Acids Res 30(14):3202–3213
Chew JL, Loh YH, Zhang W, Chen X, Tam WL, Yeap LS, Li P, Ang YS, Lim B, Robson P, Ng HH (2005) Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol Cell Biol 25(14):6031–6046. https://doi.org/10.1128/MCB.25.14.6031-6046.2005
Okumura-Nakanishi S, Saito M, Niwa H, Ishikawa F (2005) Oct-3/4 and Sox2 regulate Oct-3/4 gene in embryonic stem cells. J Biol Chem 280(7):5307–5317. https://doi.org/10.1074/jbc.M410015200
Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122(6):947–956. https://doi.org/10.1016/j.cell.2005.08.020
Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, Wong KY, Sung KW, Lee CW, Zhao XD, Chiu KP, Lipovich L, Kuznetsov VA, Robson P, Stanton LW, Wei CL, Ruan Y, Lim B, Ng HH (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38(4):431–440. https://doi.org/10.1038/ng1760
Chen X, Xu H, Yuan P, Fang F, Huss M, Vega VB, Wong E, Orlov YL, Zhang W, Jiang J, Loh YH, Yeo HC, Yeo ZX, Narang V, Govindarajan KR, Leong B, Shahab A, Ruan Y, Bourque G, Sung WK, Clarke ND, Wei CL, Ng HH (2008) Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133(6):1106–1117. https://doi.org/10.1016/j.cell.2008.04.043
Kunarso G, Chia NY, Jeyakani J, Hwang C, Lu X, Chan YS, Ng HH, Bourque G (2010) Transposable elements have rewired the core regulatory network of human embryonic stem cells. Nat Genet 42(7):631–634. https://doi.org/10.1038/ng.600
Jauch R, Aksoy I, Hutchins AP, Ng CK, Tian XF, Chen J, Palasingam P, Robson P, Stanton LW, Kolatkar PR (2011) Conversion of Sox17 into a pluripotency reprogramming factor by reengineering its association with Oct4 on DNA. Stem Cells 29(6):940–951. https://doi.org/10.1002/stem.639
Tapia N, MacCarthy C, Esch D, Gabriele Marthaler A, Tiemann U, Arauzo-Bravo MJ, Jauch R, Cojocaru V, Scholer HR (2015) Dissecting the role of distinct OCT4-SOX2 heterodimer configurations in pluripotency. Sci Rep 5:13533. https://doi.org/10.1038/srep13533
Chen J, Chen X, Li M, Liu X, Gao Y, Kou X, Zhao Y, Zheng W, Zhang X, Huo Y, Chen C, Wu Y, Wang H, Jiang C, Gao S (2016) Hierarchical Oct4 binding in concert with primed epigenetic rearrangements during somatic cell reprogramming. Cell Rep 14(6):1540–1554. https://doi.org/10.1016/j.celrep.2016.01.013
Chronis C, Fiziev P, Papp B, Butz S, Bonora G, Sabri S, Ernst J, Plath K (2017) Cooperative binding of transcription factors orchestrates reprogramming. Cell 168(3):442–459 e420. https://doi.org/10.1016/j.cell.2016.12.016
Chen J, Zhang Z, Li L, Chen BC, Revyakin A, Hajj B, Legant W, Dahan M, Lionnet T, Betzig E, Tjian R, Liu Z (2014) Single-molecule dynamics of enhanceosome assembly in embryonic stem cells. Cell 156(6):1274–1285. https://doi.org/10.1016/j.cell.2014.01.062
Jolma A, Yin Y, Nitta KR, Dave K, Popov A, Taipale M, Enge M, Kivioja T, Morgunova E, Taipale J (2015) DNA-dependent formation of transcription factor pairs alters their binding specificity. Nature 527(7578):384–388. https://doi.org/10.1038/nature15518
Dailey L, Basilico C (2001) Coevolution of HMG domains and homeodomains and the generation of transcriptional regulation by Sox/POU complexes. J Cell Physiol 186(3):315–328
Kamachi Y, Uchikawa M, Kondoh H (2000) Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet 16(4):182–187
Wilson M, Koopman P (2002) Matching SOX: partner proteins and co-factors of the SOX family of transcriptional regulators. Curr Opin Genet Dev 12(4):441–446
Kuhlbrodt K, Herbarth B, Sock E, Enderich J, Hermans-Borgmeyer I, Wegner M (1998) Cooperative function of POU proteins and SOX proteins in glial cells. J Biol Chem 273(26):16050–16057
Kuhlbrodt K, Herbarth B, Sock E, Hermans-Borgmeyer I, Wegner M (1998) Sox10, a novel transcriptional modulator in glial cells. J Neurosci 18(1):237–250
Tanaka S, Kamachi Y, Tanouchi A, Hamada H, Jing N, Kondoh H (2004) Interplay of SOX and POU factors in regulation of the Nestin gene in neural primordial cells. Mol Cell Biol 24(20):8834–8846. https://doi.org/10.1128/MCB.24.20.8834-8846.2004
Catena R, Tiveron C, Ronchi A, Porta S, Ferri A, Tatangelo L, Cavallaro M, Favaro R, Ottolenghi S, Reinbold R, Scholer H, Nicolis SK (2004) Conserved POU binding DNA sites in the Sox2 upstream enhancer regulate gene expression in embryonic and neural stem cells. J Biol Chem 279(40):41846–41857. https://doi.org/10.1074/jbc.M405514200
Lodato MA, Ng CW, Wamstad JA, Cheng AW, Thai KK, Fraenkel E, Jaenisch R, Boyer LA (2013) SOX2 co-occupies distal enhancer elements with distinct POU factors in ESCs and NPCs to specify cell state. PLoS Genet 9(2):e1003288. https://doi.org/10.1371/journal.pgen.1003288
Chang YK, Srivastava Y, Hu C, Joyce A, Yang X, Zuo Z, Havranek JJ, Stormo GD, Jauch R (2017) Quantitative profiling of selective Sox/POU pairing on hundreds of sequences in parallel by Coop-seq. Nucleic Acids Res 45(2):832–845. https://doi.org/10.1093/nar/gkw1198
Nishimoto M, Miyagi S, Yamagishi T, Sakaguchi T, Niwa H, Muramatsu M, Okuda A (2005) Oct-3/4 maintains the proliferative embryonic stem cell state via specific binding to a variant octamer sequence in the regulatory region of the UTF1 locus. Mol Cell Biol 25(12):5084–5094. https://doi.org/10.1128/MCB.25.12.5084-5094.2005
Ng CK, Li NX, Chee S, Prabhakar S, Kolatkar PR, Jauch R (2012) Deciphering the Sox–Oct partner code by quantitative cooperativity measurements. Nucleic Acids Res 40(11):4933–4941. https://doi.org/10.1093/nar/gks153
Aksoy I, Jauch R, Chen J, Dyla M, Divakar U, Bogu GK, Teo R, Leng Ng CK, Herath W, Lili S, Hutchins AP, Robson P, Kolatkar PR, Stanton LW (2013) Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm. EMBO J 32(7):938–953. https://doi.org/10.1038/emboj.2013.31
Merino F, Ng CK, Veerapandian V, Scholer HR, Jauch R, Cojocaru V (2014) Structural basis for the SOX-dependent genomic redistribution of OCT4 in stem cell differentiation. Structure 22(9):1274–1286. https://doi.org/10.1016/j.str.2014.06.014
Aksoy I, Jauch R, Eras V, Chng WB, Chen J, Divakar U, Ng CK, Kolatkar PR, Stanton LW (2013) Sox transcription factors require selective interactions with Oct4 and specific transactivation functions to mediate reprogramming. Stem Cells 31(12):2632–2646. https://doi.org/10.1002/stem.1522
Niwa H, Nakamura A, Urata M, Shirae-Kurabayashi M, Kuraku S, Russell S, Ohtsuka S (2016) The evolutionally-conserved function of group B1 Sox family members confers the unique role of Sox2 in mouse ES cells. BMC Evol Biol 16:173. https://doi.org/10.1186/s12862-016-0755-4
Irie N, Weinberger L, Tang WW, Kobayashi T, Viukov S, Manor YS, Dietmann S, Hanna JH, Surani MA (2015) SOX17 is a critical specifier of human primordial germ cell fate. Cell 160(1–2):253–268. https://doi.org/10.1016/j.cell.2014.12.013
Knaupp AS, Buckberry S, Pflueger J, Lim SM, Ford E, Larcombe MR, Rossello FJ, de Mendoza A, Alaei S, Firas J, Holmes ML, Nair SS, Clark SJ, Nefzger CM, Lister R, Polo JM (2017) Transient and permanent reconfiguration of chromatin and transcription factor occupancy drive reprogramming. Cell Stem Cell 21(6):834–845 e836. https://doi.org/10.1016/j.stem.2017.11.007
Williams DC Jr, Cai M, Clore GM (2004) Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1.Sox2.Hoxb1-DNA ternary transcription factor complex. J Biol Chem 279(2):1449–1457. https://doi.org/10.1074/jbc.M309790200
Pereira JH, Kim SH (2009) Structure of human Brn-5 transcription factor in complex with CRH gene promoter. J Struct Biol 167(2):159–165. https://doi.org/10.1016/j.jsb.2009.05.003
Esch D, Vahokoski J, Groves MR, Pogenberg V, Cojocaru V, Vom Bruch H, Han D, Drexler HC, Arauzo-Bravo MJ, Ng CK, Jauch R, Wilmanns M, Scholer HR (2013) A unique Oct4 interface is crucial for reprogramming to pluripotency. Nat Cell Biol 15(3):295–301. https://doi.org/10.1038/ncb2680
Jin W, Wang L, Zhu F, Tan W, Lin W, Chen D, Sun Q, Xia Z (2016) Critical POU domain residues confer Oct4 uniqueness in somatic cell reprogramming. Sci Rep 6:20818. https://doi.org/10.1038/srep20818
Kong X, Liu J, Li L, Yue L, Zhang L, Jiang H, Xie X, Luo C (2015) Functional interplay between the RK motif and linker segment dictates Oct4-DNA recognition. Nucleic Acids Res 43(9):4381–4392. https://doi.org/10.1093/nar/gkv323
Zaret KS, Mango SE (2016) Pioneer transcription factors, chromatin dynamics, and cell fate control. Curr Opin Genet Dev 37:76–81. https://doi.org/10.1016/j.gde.2015.12.003
Gualdi R, Bossard P, Zheng M, Hamada Y, Coleman JR, Zaret KS (1996) Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control. Genes Dev 10(13):1670–1682
Caravaca JM, Donahue G, Becker JS, He X, Vinson C, Zaret KS (2013) Bookmarking by specific and nonspecific binding of FoxA1 pioneer factor to mitotic chromosomes. Genes Dev 27(3):251–260. https://doi.org/10.1101/gad.206458.112
Clark KL, Halay ED, Lai E, Burley SK (1993) Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. Nature 364(6436):412–420. https://doi.org/10.1038/364412a0
Ramakrishnan V, Finch JT, Graziano V, Lee PL, Sweet RM (1993) Crystal structure of globular domain of histone H5 and its implications for nucleosome binding. Nature 362(6417):219–223. https://doi.org/10.1038/362219a0
Cirillo LA, McPherson CE, Bossard P, Stevens K, Cherian S, Shim EY, Clark KL, Burley SK, Zaret KS (1998) Binding of the winged-helix transcription factor HNF3 to a linker histone site on the nucleosome. EMBO J 17(1):244–254. https://doi.org/10.1093/emboj/17.1.244
Bednar J, Garcia-Saez I, Boopathi R, Cutter AR, Papai G, Reymer A, Syed SH, Lone IN, Tonchev O, Crucifix C, Menoni H, Papin C, Skoufias DA, Kurumizaka H, Lavery R, Hamiche A, Hayes JJ, Schultz P, Angelov D, Petosa C, Dimitrov S (2017) Structure and dynamics of a 197 bp nucleosome in complex with linker histone H1. Mol Cell 66(3):384–397 e388. https://doi.org/10.1016/j.molcel.2017.04.012
Song F, Chen P, Sun D, Wang M, Dong L, Liang D, Xu RM, Zhu P, Li G (2014) Cryo-EM study of the chromatin fiber reveals a double helix twisted by tetranucleosomal units. Science 344(6182):376–380. https://doi.org/10.1126/science.1251413
Cirillo LA, Lin FR, Cuesta I, Friedman D, Jarnik M, Zaret KS (2002) Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4. Mol Cell 9(2):279–289
Soufi A, Donahue G, Zaret KS (2012) Facilitators and impediments of the pluripotency reprogramming factors’ initial engagement with the genome. Cell 151(5):994–1004. https://doi.org/10.1016/j.cell.2012.09.045
Soufi A, Garcia MF, Jaroszewicz A, Osman N, Pellegrini M, Zaret KS (2015) Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming. Cell 161(3):555–568. https://doi.org/10.1016/j.cell.2015.03.017
Zviran A, Mor N, Rais Y, Gingold H, Peles S, Chomsky E, Viukov S, Buenrostro JD, Weinberger L, Manor YS, Krupalnik V, Zerbib M, Hezroni H, Jaitin DA, Larastiaso D, Gilad S, Benjamin S, Mousa A, Ayyash M, Sheban D, Bayerl J, Castrejon AA, Massarwa R, Maza I, Hanna S, Amit I, Stelzer Y, Ulitsky I, Greenleaf WJ, Pilpel Y, Novershtern N, Hanna JH (2017) High-resolution dissection of conducive reprogramming trajectory to ground state pluripotency. bioRxiv. https://doi.org/10.1101/184135
Li D, Liu J, Yang X, Zhou C, Guo J, Wu C, Qin Y, Guo L, He J, Yu S, Liu H, Wang X, Wu F, Kuang J, Hutchins AP, Chen J, Pei D (2017) Chromatin accessibility dynamics during iPSC reprogramming. Cell Stem Cell 21(6):819–833 e816. https://doi.org/10.1016/j.stem.2017.10.012
Swinstead EE, Paakinaho V, Presman DM, Hager GL (2016) Pioneer factors and ATP-dependent chromatin remodeling factors interact dynamically: a new perspective: Multiple transcription factors can effect chromatin pioneer functions through dynamic interactions with ATP-dependent chromatin remodeling factors. BioEssays 38(11):1150–1157. https://doi.org/10.1002/bies.201600137
Zaret KS, Lerner J, Iwafuchi-Doi M (2016) Chromatin scanning by dynamic binding of pioneer factors. Mol Cell 62(5):665–667. https://doi.org/10.1016/j.molcel.2016.05.024
Panne D, Maniatis T, Harrison SC (2007) An atomic model of the interferon-beta enhanceosome. Cell 129(6):1111–1123. https://doi.org/10.1016/j.cell.2007.05.019
Kagey MH, Newman JJ, Bilodeau S, Zhan Y, Orlando DA, van Berkum NL, Ebmeier CC, Goossens J, Rahl PB, Levine SS, Taatjes DJ, Dekker J, Young RA (2010) Mediator and cohesin connect gene expression and chromatin architecture. Nature 467(7314):430–435. https://doi.org/10.1038/nature09380
Nozawa K, Schneider TR, Cramer P (2017) Core mediator structure at 3.4 A extends model of transcription initiation complex. Nature 545(7653):248–251. https://doi.org/10.1038/nature22328
Azuara V, Perry P, Sauer S, Spivakov M, Jorgensen HF, John RM, Gouti M, Casanova M, Warnes G, Merkenschlager M, Fisher AG (2006) Chromatin signatures of pluripotent cell lines. Nat Cell Biol 8(5):532–538. https://doi.org/10.1038/ncb1403
Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125(2):315–326. https://doi.org/10.1016/j.cell.2006.02.041
Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O’Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, Bernstein BE (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448(7153):553–560. https://doi.org/10.1038/nature06008
Koche RP, Smith ZD, Adli M, Gu H, Ku M, Gnirke A, Bernstein BE, Meissner A (2011) Reprogramming factor expression initiates widespread targeted chromatin remodeling. Cell Stem Cell 8(1):96–105. https://doi.org/10.1016/j.stem.2010.12.001
Ang YS, Tsai SY, Lee DF, Monk J, Su J, Ratnakumar K, Ding J, Ge Y, Darr H, Chang B, Wang J, Rendl M, Bernstein E, Schaniel C, Lemischka IR (2011) Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network. Cell 145(2):183–197. https://doi.org/10.1016/j.cell.2011.03.003
Mansour AA, Gafni O, Weinberger L, Zviran A, Ayyash M, Rais Y, Krupalnik V, Zerbib M, Amann-Zalcenstein D, Maza I, Geula S, Viukov S, Holtzman L, Pribluda A, Canaani E, Horn-Saban S, Amit I, Novershtern N, Hanna JH (2012) The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming. Nature 488(7411):409–413. https://doi.org/10.1038/nature11272
Brumbaugh J, Hou Z, Russell JD, Howden SE, Yu P, Ledvina AR, Coon JJ, Thomson JA (2012) Phosphorylation regulates human OCT4. Proc Natl Acad Sci USA 109(19):7162–7168. https://doi.org/10.1073/pnas.1203874109
Kang J, Gemberling M, Nakamura M, Whitby FG, Handa H, Fairbrother WG, Tantin D (2009) A general mechanism for transcription regulation by Oct1 and Oct4 in response to genotoxic and oxidative stress. Genes Dev 23(2):208–222. https://doi.org/10.1101/gad.1750709
Lin Y, Yang Y, Li W, Chen Q, Li J, Pan X, Zhou L, Liu C, Chen C, He J, Cao H, Yao H, Zheng L, Xu X, Xia Z, Ren J, Xiao L, Li L, Shen B, Zhou H, Wang YJ (2012) Reciprocal regulation of Akt and Oct4 promotes the self-renewal and survival of embryonal carcinoma cells. Mol Cell 48(4):627–640. https://doi.org/10.1016/j.molcel.2012.08.030
Nieto L, Joseph G, Stella A, Henri P, Burlet-Schiltz O, Monsarrat B, Clottes E, Erard M (2007) Differential effects of phosphorylation on DNA binding properties of N Oct-3 are dictated by protein/DNA complex structures. J Mol Biol 370(4):687–700. https://doi.org/10.1016/j.jmb.2007.04.072
Schild-Poulter C, Shih A, Tantin D, Yarymowich NC, Soubeyrand S, Sharp PA, Hache RJ (2007) DNA-PK phosphorylation sites on Oct-1 promote cell survival following DNA damage. Oncogene 26(27):3980–3988. https://doi.org/10.1038/sj.onc.1210165
Segil N, Roberts SB, Heintz N (1991) Mitotic phosphorylation of the Oct-1 homeodomain and regulation of Oct-1 DNA binding activity. Science 254(5039):1814–1816
Jang H, Kim TW, Yoon S, Choi SY, Kang TW, Kim SY, Kwon YW, Cho EJ, Youn HD (2012) O-GlcNAc regulates pluripotency and reprogramming by directly acting on core components of the pluripotency network. Cell Stem Cell 11(1):62–74. https://doi.org/10.1016/j.stem.2012.03.001
Kang J, Shen Z, Lim JM, Handa H, Wells L, Tantin D (2013) Regulation of Oct1/Pou2f1 transcription activity by O-GlcNAcylation. FASEB J 27(7):2807–2817. https://doi.org/10.1096/fj.12-220897
Webster DM, Teo CF, Sun Y, Wloga D, Gay S, Klonowski KD, Wells L, Dougan ST (2009) O-GlcNAc modifications regulate cell survival and epiboly during zebrafish development. BMC Dev Biol 9:28. https://doi.org/10.1186/1471-213X-9-28
Wei F, Scholer HR, Atchison ML (2007) Sumoylation of Oct4 enhances its stability, DNA binding, and transactivation. J Biol Chem 282(29):21551–21560. https://doi.org/10.1074/jbc.M611041200
Zhang Z, Liao B, Xu M, Jin Y (2007) Post-translational modification of POU domain transcription factor Oct-4 by SUMO-1. FASEB J 21(12):3042–3051. https://doi.org/10.1096/fj.06-6914com
Kang J, Goodman B, Zheng Y, Tantin D (2011) Dynamic regulation of Oct1 during mitosis by phosphorylation and ubiquitination. PLoS One 6(8):e23872. https://doi.org/10.1371/journal.pone.0023872
Xu HM, Liao B, Zhang QJ, Wang BB, Li H, Zhong XM, Sheng HZ, Zhao YX, Zhao YM, Jin Y (2004) Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination. J Biol Chem 279(22):23495–23503. https://doi.org/10.1074/jbc.M400516200
Saxe JP, Tomilin A, Scholer HR, Plath K, Huang J (2009) Post-translational regulation of Oct4 transcriptional activity. PLoS One 4(2):e4467. https://doi.org/10.1371/journal.pone.0004467
Lai JS, Cleary MA, Herr W (1992) A single amino acid exchange transfers VP16-induced positive control from the Oct-1 to the Oct-2 homeo domain. Genes Dev 6(11):2058–2065
Pomerantz JL, Kristie TM, Sharp PA (1992) Recognition of the surface of a homeo domain protein. Genes Dev 6(11):2047–2057
Dawson SJ, Palmer RD, Morris PJ, Latchman DS (1998) Functional role of position 22 in the homeodomain of Brn-3 transcription factors. NeuroReport 9(10):2305–2309
Fowler DM, Fields S (2014) Deep mutational scanning: a new style of protein science. Nat Methods 11(8):801–807. https://doi.org/10.1038/nmeth.3027
Ding J, Xu H, Faiola F, Ma’ayan A, Wang J (2012) Oct4 links multiple epigenetic pathways to the pluripotency network. Cell Res 22(1):155–167. https://doi.org/10.1038/cr.2011.179
Pardo M, Lang B, Yu L, Prosser H, Bradley A, Babu MM, Choudhary J (2010) An expanded Oct4 interaction network: implications for stem cell biology, development, and disease. Cell Stem Cell 6(4):382–395. https://doi.org/10.1016/j.stem.2010.03.004
van den Berg DL, Snoek T, Mullin NP, Yates A, Bezstarosti K, Demmers J, Chambers I, Poot RA (2010) An Oct4-centered protein interaction network in embryonic stem cells. Cell Stem Cell 6(4):369–381. https://doi.org/10.1016/j.stem.2010.02.014
Arnold CD, Gerlach D, Stelzer C, Boryn LM, Rath M, Stark A (2013) Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science 339(6123):1074–1077. https://doi.org/10.1126/science.1232542
Farnung L, Vos SM, Wigge C, Cramer P (2017) Nucleosome-Chd1 structure and implications for chromatin remodelling. Nature 550(7677):539–542. https://doi.org/10.1038/nature24046
Yang X, Malik V, Jauch R (2015) Reprogramming cells with synthetic proteins. Asian J Androl 17(3):394–402. https://doi.org/10.4103/1008-682X.145433
Tsubooka N, Ichisaka T, Okita K, Takahashi K, Nakagawa M, Yamanaka S (2009) Roles of Sall4 in the generation of pluripotent stem cells from blastocysts and fibroblasts. Genes Cells 14(6):683–694. https://doi.org/10.1111/j.1365-2443.2009.01301.x
Maekawa M, Yamaguchi K, Nakamura T, Shibukawa R, Kodanaka I, Ichisaka T, Kawamura Y, Mochizuki H, Goshima N, Yamanaka S (2011) Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1. Nature 474(7350):225–229. https://doi.org/10.1038/nature10106
Wernig M, Meissner A, Cassady JP, Jaenisch R (2008) c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell 2(1):10–12. https://doi.org/10.1016/j.stem.2007.12.001
Feng B, Jiang J, Kraus P, Ng JH, Heng JC, Chan YS, Yaw LP, Zhang W, Loh YH, Han J, Vega VB, Cacheux-Rataboul V, Lim B, Lufkin T, Ng HH (2009) Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat Cell Biol 11(2):197–203. https://doi.org/10.1038/ncb1827
Maherali N, Hochedlinger K (2009) Tgfbeta signal inhibition cooperates in the induction of iPSCs and replaces Sox2 and cMyc. Curr Biol 19(20):1718–1723. https://doi.org/10.1016/j.cub.2009.08.025
Lyssiotis CA, Foreman RK, Staerk J, Garcia M, Mathur D, Markoulaki S, Hanna J, Lairson LL, Charette BD, Bouchez LC, Bollong M, Kunick C, Brinker A, Cho CY, Schultz PG, Jaenisch R (2009) Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4. Proc Natl Acad Sci USA 106(22):8912–8917. https://doi.org/10.1073/pnas.0903860106
Kawamura T, Suzuki J, Wang YV, Menendez S, Morera LB, Raya A, Wahl GM, Izpisua Belmonte JC (2009) Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460(7259):1140–1144. https://doi.org/10.1038/nature08311
Chen J, Liu J, Yang J, Chen Y, Chen J, Ni S, Song H, Zeng L, Ding K, Pei D (2011) BMPs functionally replace Klf4 and support efficient reprogramming of mouse fibroblasts by Oct4 alone. Cell Res 21(1):205–212. https://doi.org/10.1038/cr.2010.172
Moon JH, Heo JS, Kim JS, Jun EK, Lee JH, Kim A, Kim J, Whang KY, Kang YK, Yeo S, Lim HJ, Han DW, Kim DW, Oh S, Yoon BS, Scholer HR, You S (2011) Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1. Cell Res 21(9):1305–1315. https://doi.org/10.1038/cr.2011.107
Shi Y, Desponts C, Do JT, Hahm HS, Scholer HR, Ding S (2008) Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 3(5):568–574. https://doi.org/10.1016/j.stem.2008.10.004
Li Y, Zhang Q, Yin X, Yang W, Du Y, Hou P, Ge J, Liu C, Zhang W, Zhang X, Wu Y, Li H, Liu K, Wu C, Song Z, Zhao Y, Shi Y, Deng H (2011) Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules. Cell Res 21(1):196–204. https://doi.org/10.1038/cr.2010.142
Tsai SY, Bouwman BA, Ang YS, Kim SJ, Lee DF, Lemischka IR, Rendl M (2011) Single transcription factor reprogramming of hair follicle dermal papilla cells to induced pluripotent stem cells. Stem Cells 29(6):964–971. https://doi.org/10.1002/stem.649
Tsai SY, Clavel C, Kim S, Ang YS, Grisanti L, Lee DF, Kelley K, Rendl M (2010) Oct4 and klf4 reprogram dermal papilla cells into induced pluripotent stem cells. Stem Cells 28(2):221–228. https://doi.org/10.1002/stem.281
Eminli S, Foudi A, Stadtfeld M, Maherali N, Ahfeldt T, Mostoslavsky G, Hock H, Hochedlinger K (2009) Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nat Genet 41(9):968–976. https://doi.org/10.1038/ng.428
Sugii S, Kida Y, Kawamura T, Suzuki J, Vassena R, Yin YQ, Lutz MK, Berggren WT, Izpisua Belmonte JC, Evans RM (2010) Human and mouse adipose-derived cells support feeder-independent induction of pluripotent stem cells. Proc Natl Acad Sci USA 107(8):3558–3563. https://doi.org/10.1073/pnas.0910172106
Wu T, Wang H, He J, Kang L, Jiang Y, Liu J, Zhang Y, Kou Z, Liu L, Zhang X, Gao S (2011) Reprogramming of trophoblast stem cells into pluripotent stem cells by Oct4. Stem Cells 29(5):755–763. https://doi.org/10.1002/stem.617
Shi Y, Do JT, Desponts C, Hahm HS, Scholer HR, Ding S (2008) A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell 2(6):525–528. https://doi.org/10.1016/j.stem.2008.05.011
Silva J, Barrandon O, Nichols J, Kawaguchi J, Theunissen TW, Smith A (2008) Promotion of reprogramming to ground state pluripotency by signal inhibition. PLoS Biol 6(10):e253. https://doi.org/10.1371/journal.pbio.0060253
Kim JB, Zaehres H, Wu G, Gentile L, Ko K, Sebastiano V, Arauzo-Bravo MJ, Ruau D, Han DW, Zenke M, Scholer HR (2008) Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 454(7204):646–650. https://doi.org/10.1038/nature07061
Utikal J, Maherali N, Kulalert W, Hochedlinger K (2009) Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells. J Cell Sci 122(Pt 19):3502–3510. https://doi.org/10.1242/jcs.054783
Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K, Takahashi K, Chiba T, Yamanaka S (2008) Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 321(5889):699–702. https://doi.org/10.1126/science.1154884
Hanna J, Markoulaki S, Schorderet P, Carey BW, Beard C, Wernig M, Creyghton MP, Steine EJ, Cassady JP, Foreman R, Lengner CJ, Dausman JA, Jaenisch R (2008) Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 133(2):250–264. https://doi.org/10.1016/j.cell.2008.03.028
Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K (2008) Induced pluripotent stem cells generated without viral integration. Science 322(5903):945–949. https://doi.org/10.1126/science.1162494
Tan KY, Eminli S, Hettmer S, Hochedlinger K, Wagers AJ (2011) Efficient generation of iPS cells from skeletal muscle stem cells. PLoS One 6(10):e26406. https://doi.org/10.1371/journal.pone.0026406
Lowry WE, Richter L, Yachechko R, Pyle AD, Tchieu J, Sridharan R, Clark AT, Plath K (2008) Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci USA 105(8):2883–2888. https://doi.org/10.1073/pnas.0711983105
Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451(7175):141–146. https://doi.org/10.1038/nature06534
Zhao Y, Yin X, Qin H, Zhu F, Liu H, Yang W, Zhang Q, Xiang C, Hou P, Song Z, Liu Y, Yong J, Zhang P, Cai J, Liu M, Li H, Li Y, Qu X, Cui K, Zhang W, Xiang T, Wu Y, Zhao Y, Liu C, Yu C, Yuan K, Lou J, Ding M, Deng H (2008) Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell 3(5):475–479. https://doi.org/10.1016/j.stem.2008.10.002
Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, Muhlestein W, Melton DA (2008) Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol 26(11):1269–1275. https://doi.org/10.1038/nbt.1502
Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A, Gonzalez F, Vassena R, Bilic J, Pekarik V, Tiscornia G, Edel M, Boue S, Izpisua Belmonte JC (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol 26(11):1276–1284. https://doi.org/10.1038/nbt.1503
Maherali N, Ahfeldt T, Rigamonti A, Utikal J, Cowan C, Hochedlinger K (2008) A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell 3(3):340–345. https://doi.org/10.1016/j.stem.2008.08.003
Yan X, Qin H, Qu C, Tuan RS, Shi S, Huang GT (2010) iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin. Stem Cells Dev 19(4):469–480. https://doi.org/10.1089/scd.2009.0314
Li H, Collado M, Villasante A, Strati K, Ortega S, Canamero M, Blasco MA, Serrano M (2009) The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460(7259):1136–1139. https://doi.org/10.1038/nature08290
Zhao HX, Li Y, Jin HF, Xie L, Liu C, Jiang F, Luo YN, Yin GW, Li Y, Wang J, Li LS, Yao YQ, Wang XH (2010) Rapid and efficient reprogramming of human amnion-derived cells into pluripotency by three factors OCT4/SOX2/NANOG. Differentiation 80(2–3):123–129. https://doi.org/10.1016/j.diff.2010.03.002
Haase A, Olmer R, Schwanke K, Wunderlich S, Merkert S, Hess C, Zweigerdt R, Gruh I, Meyer J, Wagner S, Maier LS, Han DW, Glage S, Miller K, Fischer P, Scholer HR, Martin U (2009) Generation of induced pluripotent stem cells from human cord blood. Cell Stem Cell 5(4):434–441. https://doi.org/10.1016/j.stem.2009.08.021
Giorgetti A, Montserrat N, Aasen T, Gonzalez F, Rodriguez-Piza I, Vassena R, Raya A, Boue S, Barrero MJ, Corbella BA, Torrabadella M, Veiga A, Izpisua Belmonte JC (2009) Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2. Cell Stem Cell 5(4):353–357. https://doi.org/10.1016/j.stem.2009.09.008
Liu H, Ye Z, Kim Y, Sharkis S, Jang YY (2010) Generation of endoderm-derived human induced pluripotent stem cells from primary hepatocytes. Hepatology 51(5):1810–1819. https://doi.org/10.1002/hep.23626
Aoki T, Ohnishi H, Oda Y, Tadokoro M, Sasao M, Kato H, Hattori K, Ohgushi H (2010) Generation of induced pluripotent stem cells from human adipose-derived stem cells without c-MYC. Tissue Eng Part A 16(7):2197–2206. https://doi.org/10.1089/ten.TEA.2009.0747
Bar-Nur O, Russ HA, Efrat S, Benvenisty N (2011) Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell 9(1):17–23. https://doi.org/10.1016/j.stem.2011.06.007
Acknowledgements
We thank Andrew Hutchins, Sergiy Velychko for discussions and Yogesh Srivastava for help with structural models. R.J. is supported by the Ministry of Science and Technology of China (2013DFE33080, 2016YFA0100700, 2017YFA0105103) by the National Natural Science Foundation of China (Grant No. 31471238), a 100 talent award of the Chinese Academy of Sciences and by a Science and Technology Planning Projects of Guangdong Province, China (2017B030314056 and 2016A050503038). V.M. thanks the CAS-TWAS (Chinese Academy of Sciences–The World Academy of Sciences) President’s Fellowship and UCAS (University of Chinese Academy of Science) for financial and infrastructure support.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Malik, V., Zimmer, D. & Jauch, R. Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming. Cell. Mol. Life Sci. 75, 1587–1612 (2018). https://doi.org/10.1007/s00018-018-2748-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00018-018-2748-5