Cell
Volume 50, Issue 6, 11 September 1987, Pages 847-861
Journal home page for Cell

Article
Positive and negative regulation of transcription in vitro: Enhancer-binding protein AP-2 is inhibited by SV40 T antigen

https://doi.org/10.1016/0092-8674(87)90512-5Get rights and content

Abstract

We have purified a 52 kd protein, AP-2, that binds to enhancer regions of SV40 and human metallothionein IIA (hMT IIA) and stimulates RNA synthesis from these promoters in vitro. Surprisingly, AP-2 also binds to two SV40 early promoter regions recognized by Sp1 and T antigen. Juxtaposed binding sites for AP-2 and Sp1 in the 21 bp repeats may facilitate productive interactions between the two factors. In contrast, sequence-specific binding of AP-2 to SV40 and hMT IIA DNA is inhibited by the viral repressor protein T antigen. Furthermore, T antigen inhibits AP-2-dependent transcriptional activation of the hMT IIA promoter in vitro. The inhibition is neither a direct nor an indirect result of T antigen binding to DNA, because the hMT IIA promoter lacks T antigen binding sites. Instead, sedimentation studies suggest that protein-protein interactions between AP-2 and T antigen block AP-2 binding to DNA. These findings suggest novel mechanisms for mediating positive and negative regulation of transcription.

References (53)

  • A.M. Maxam et al.

    Sequencing end-labeled DNA with base-specific chemical cleavages

    Meth. Enzymol.

    (1980)
  • R.M. Myers et al.

    SV40 gene expression is modulated by the cooperative binding of T antigen to DNA

    Cell

    (1981)
  • D.C. Rio et al.

    SV40 T antigen binding site mutations that affect autoregulation

    Cell

    (1983)
  • C. Schneider et al.

    A one-step purification of membrane proteins using a high efficiency immunomatrix

    J. Biol. Chem.

    (1982)
  • R. Sen et al.

    Inducibility of κ immunoglobulin enhancer-binding protein NF-κB by a posttranslational mechanism

    Cell

    (1986)
  • R. Sen et al.

    Multiple nuclear factors interact with the immunoglobulin enhancer sequences

    Cell

    (1986)
  • E. Serfling et al.

    Enhancers and eukaryotic gene transcription

    Trends in Genet.

    (1985)
  • C. Thummel et al.

    Translational control of SV40 T antigen expressed from the adenovirus late promoter

    Cell

    (1983)
  • R. Treisman

    Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors

    Cell

    (1986)
  • A. Velcich et al.

    Adenovirus E1a proteins repress transcription from the SV40 early promoter

    Cell

    (1985)
  • G. Wiederrecht et al.

    The Saccharomyces and Drosophila heat shock transcription factors are identical in size and DNA binding properties

    Cell

    (1987)
  • E. Borrelli et al.

    Adenovirus-2 E1a products repress enhancer-induced stimulation of transcription

    Nature

    (1984)
  • M.R. Briggs et al.

    Purification and biochemical characterization of the promoter-specific transcription factor, Sp1

    Science

    (1986)
  • M. Comb et al.

    A cyclic AMP- and phorbol ester-inducible DNA element

    Nature

    (1986)
  • I. Davidson et al.

    Cell-type specific protein binding to the enhancer of simian virus 40 in nuclear extracts

    Nature

    (1986)
  • D. DeFranco et al.

    Two different factors act separately or together to specify functionally distinct activities at a single transcriptional enhancer

    Mol. Cell. Biol.

    (1986)
  • Cited by (786)

    • An Osteoporosis Risk SNP at 1p36.12 Acts as an Allele-Specific Enhancer to Modulate LINC00339 Expression via Long-Range Loop Formation

      2018, American Journal of Human Genetics
      Citation Excerpt :

      Our results indicated that TFAP2A could particularly bind to rs6426749-G allele to increase the expression of LINC00339. TFAP2A is a transcriptional activator that can bind to enhancer regions to elevate the enhancer activities.70,71 Our knockdown experiment found that downregulation of TFAP2A efficiently repressed LINC00339 expression in osteoblast cells, which provides functional evidence to support the role of transcriptional activation for TFAP2A.

    View all citing articles on Scopus
    View full text