p300 provides a corepressor function by cooperating with YY1 and HDAC3 to repress c-Myc

N. Sankar, S. Baluchamy, R. K. Kadeppagari, G. Singhal, S. Weitzman, B. Thimmapaya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

We showed earlier that p300/CBP plays an important role in G1 progression by negatively regulating c-Myc and thereby preventing premature G1 exit. Here, we have studied the mechanism by which p300 represses c-Myc and show that in quiescent cells p300 cooperates with histone deacetylase 3 (HDAC3) to repress transcription. p300 and HDAC3 are recruited to the upstream YY1-binding site of the c-Myc promoter resulting in chromatin deacetylation and repression of c-Myc transcription. Consistent with this, ablation of p300, YY1 or HDAC3 expression results in chromatin acetylation and induction of c-Myc. These three proteins exist as a complex in vivo and form a multiprotein complex with the YY1-binding site in vitro. The C-terminal region of p300 is both necessary and sufficient for the repression of c-Myc. These and other results suggest that in quiescent cells the C-terminal region of p300 provides corepressor function and facilitates the recruitment of p300 and HDAC3 to the YY1-binding site and represses the c-Myc promoter. This corepressor function of p300 prevents the inappropriate induction of c-Myc and S phase.

Original languageEnglish (US)
Pages (from-to)5717-5728
Number of pages12
JournalOncogene
Volume27
Issue number43
DOIs
StatePublished - Sep 25 2008

Keywords

  • Cell cycle
  • Gene expression
  • HDAC3
  • YY1
  • c-Myc
  • p300

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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