title: Selective roles for cAMP response element-binding protein binding protein and p300 protein as coregulators for androgen-regulated gene expression in advanced prostate cancer cells.
abstract: The protein acetyltransferases p300 and cAMP response element-binding protein binding protein (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, whereas, 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 TATA box binding protein (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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089-9176, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Ianculescu
authors.forename: Dai-Ying
authors.initials: DY
authors.lastname: Wu
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Siegmund
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stallcup
mesh_terms: D000728:Androgens / Q000378:metabolism / Q000494:pharmacology*; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D000728:Androgens; D050882:CREB-Binding Protein; D006657:Histones; D009363:Neoplasm Proteins; D017430:Prostate-Specific Antigen; D012697:Serine Endopeptidases; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C494363:CREBBP protein, human; C421305:TMPRSS2 protein, human