Dynamic methylation of histone H3 at lysine 4 in transcriptional regulation by the androgen receptor

Abstract

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 tri-methylated 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 ∼4 h. The results suggest a novel role of methylated H3-K4 in transcriptional regulation.