The protein acetyltransferases p300 and CBP are homologous, ubiquitously expressed proteins that interact with hundreds of proteins involved in transcriptional regulation and are involved globally as transcriptional coregulators. Although these two proteins acetylate and interact with overlapping sets of proteins, we found that p300 and CBP contribute to androgen-induced regulation of distinct sets of genes in C4-2B prostate cancer cells, a model of advanced prostate cancer. CBP cannot compensate for the loss of p300 to support androgen-induced expression of many genes, such as TMPRSS2 and PSA. Global gene expression analysis indicated that 47% of androgen regulated genes are p300 dependent in these cells, while surprisingly only 0.3% of them are CBP dependent. Chromatin immunoprecipitation analysis after depletion of cellular p300 indicated that p300 is required for androgen-induced acetylation of histones H3 and H4, methylation of histone H3 at Lys 4, and recruitment of TBP and RNA polymerase II, but not recruitment of the androgen receptor, on the TMPRSS2 gene in response to androgen. Thus, p300 is the dominant coregulator of the CBP/p300 pair for androgen-regulated gene expression in C4-2B cells. p300 is required at an early stage of chromatin remodeling and transcription complex assembly, after binding of androgen receptor to the gene but before many critical histone modifications occur.
Written by:
Ianculescu I, Wu DY, Siegmund KD, Stallcup MR. Are you the author?
University of Southern California, United States.
Reference: J Biol Chem. 2011 Dec 15. Epub ahead of print.
doi: 10.1074/jbc.M111.300194
PubMed Abstract
PMID: 22174411
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