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Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming

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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.

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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.

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  1. CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, 511436, China

    Vikas Malik, Dennis Zimmer & Ralf Jauch

  2. Genome Regulation Laboratory, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China

    Vikas Malik, Dennis Zimmer & Ralf Jauch

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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

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