Dynamic methylation of histone H3 at lysine 4 in transcriptional regulation by the androgen receptor.
The methylation of histone H3 correlates with either gene expression or silencing depending on the residues modified. Methylated lysine 4 (H3-K4) is associated with transcription at active gene loci. Furthermore, it was reported that trimethylated but not dimethylated H3-K4 is exclusively associated with active chromatin in Saccharomyces cerevisiae. In the present study, we investigated the H3-K4 methylation at the human prostate specific antigen (PSA) locus following gene activation and repression via androgen receptor (AR). We show that ligand-induced, AR-mediated transcription was accompanied by rapid decreases in di- and trimethylated H3-K4 at the PSA enhancer and promoter. Moreover, the observed decreases in H3-K4 methylation were reversed when AR was inhibited by a specific AR antagonist, bicalutamide. In contrast to the decreases in methylation at the 5' transcriptional control regions of the PSA gene, H3-K4 methylation in the coding region steadily increased after a lag period of approximately 4 h. The results suggest a novel role of methylated H3-K4 in transcriptional regulation.
Kim
Joshua
J
Department of Urology, Norris Cancer Center, USC Keck School of Medicine, Los Angeles, CA 90089, USA.
Jia
Li
L
Tilley
Wayne D
WD
Coetzee
Gerhard A
GA
D059002:Androgen Receptor Antagonists; D000813:Anilides / Q000494:pharmacology; D045744:Cell Line, Tumor; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005091:Exons / Q000235:genetics; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000378:metabolism*; D008297:Male; D008745:Methylation / Q000187:drug effects; D009570:Nitriles; D011401:Promoter Regions, Genetic / Q000235:genetics; D017430:Prostate-Specific Antigen / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D014105:Tosyl Compounds; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
D059002:Androgen Receptor Antagonists; D000813:Anilides; D006657:Histones; D009570:Nitriles; D012333:RNA, Messenger; D011944:Receptors, Androgen; D014105:Tosyl Compounds; C053541:bicalutamide; D017430:Prostate-Specific Antigen; D008239:Lysine