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

Oncogene volume 27, pages 5717–5728 (2008)Cite this article

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.

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Acknowledgements

We are very grateful to Drs E Seto (Moffits Cancer Center), Dr Wu (University of Oregon), Yang Shi (Harvard University), N Perkins and R Hayward (University of Dundee, UK), and G Chinnadurai (St Louis University) for providing various plasmids and viruses. We also thank Dr Kathy Rundell for helpful discussion and editing this article. This work was supported by the NIH Grant CA73303.

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Author notes

  1. S Baluchamy

    Present address: 4Current address: University of Illinois School of Medicine, Chicago, IL, USA.,

  2. R-K Kadeppagari

    Present address: 5Current address: LSU Health Sciences Center, New Orleans, LA, USA.,

  3. S Baluchamy, R-K Kadeppagari and G Singhal: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    N Sankar, S Baluchamy, R-K Kadeppagari, G Singhal & B Thimmapaya

  2. Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    S Weitzman

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  1. N Sankar
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Correspondence to B Thimmapaya.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Sankar, N., Baluchamy, S., Kadeppagari, RK. et al. p300 provides a corepressor function by cooperating with YY1 and HDAC3 to repress c-Myc. Oncogene 27, 5717–5728 (2008). https://doi.org/10.1038/onc.2008.181

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