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Selective roles for cAMP response element-binding protein binding protein and p300 protein as coregulators for

Irina Ianculescu1, Dai-Ying Wu, Kimberly D Siegmund

  • 1Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089-9176, USA.

The Journal of Biological Chemistry
|December 17, 2011
PubMed

Insights

The protein p300, not CBP, is crucial for androgen-regulated gene expression in advanced prostate cancer cells. P300 controls key steps in gene activation, including histone modifications and transcription complex assembly.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • p300 and CBP are homologous transcriptional coregulators involved in gene regulation.
  • They acetylate and interact with overlapping sets of proteins.
  • Their specific roles in androgen-induced gene regulation in prostate cancer are not fully understood.

Purpose of the Study:

  • To investigate the distinct roles of p300 and CBP in androgen-regulated gene expression in C4-2B prostate cancer cells.
  • To determine the dependency of androgen-regulated genes on p300 and CBP.
  • To elucidate the molecular mechanisms by which p300 influences androgen-induced gene expression.

Main Methods:

  • Global gene expression analysis (microarray or RNA-Seq).
  • Chromatin immunoprecipitation (ChIP) assays.
  • Depletion of p300 using siRNA or shRNA.

Main Results:

  • p300 and CBP regulate distinct gene sets in response to androgen.
  • 47% of androgen-regulated genes are p300-dependent, while only 0.3% are CBP-dependent.
  • p300 is essential for androgen-induced histone acetylation (H3, H4), H3 Lys-4 methylation, and recruitment of TBP and RNA polymerase II to the TMPRSS2 gene.

Conclusions:

  • p300 is the dominant coregulator of the CBP/p300 pair for androgen-regulated gene expression in C4-2B cells.
  • p300 acts early in the process, facilitating chromatin remodeling and transcription complex assembly after androgen receptor binding.
  • CBP cannot compensate for p300 loss in supporting androgen-induced expression of key genes like TMPRSS2 and PSA.

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