Nucleic Acids Research, 2003, Vol. 31, No. 23 6741-6747
© 2003 Oxford University Press
Article |
Dynamic methylation of histone H3 at lysine 4 in transcriptional regulation by the androgen receptor
1 Department of Urology, 2 Department of Molecular Microbiology and 3 Department of Preventive Medicine, Norris Cancer Center, USC Keck School of Medicine, Los Angeles, CA 90089, USA and 4 Department of Medicine, University of Adelaide and Hanson Institute, Adelaide, SA, Australia
*To whom correspondence should be addressed. Tel: +1 323 865 0631; Fax: +1 323 865 0634; Email: coetzee{at}usc.edu
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
4 h. The results suggest a novel role of methylated H3-K4 in transcriptional regulation.
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