JHDM2A, a JmjC-Containing H3K9 Demethylase, Facilitates Transcription Activation by Androgen Receptor

Kenichi Yamane, Charalambos Toumazou, Yu ichi Tsukada, Hediye Erdjument-Bromage, Paul Tempst, Jiemin Wong, Yi Zhang

Research output: Contribution to journalArticle

577 Citations (Scopus)

Abstract

Covalent modification of histones plays an important role in regulating chromatin dynamics and transcription. Histone methylation was thought to be an irreversible modification until recently. Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. Similar to JHDM1, JHDM2A-mediated histone demethylation requires cofactors Fe(II) and α-ketoglutarate. Mutational studies indicate that a JmjC domain and a zinc finger present in JHDM2A are required for its enzymatic activity. Overexpression of JHDM2A greatly reduced the H3K9 methylation level in vivo. Knockdown of JHDM2A results in an increase in the dimethyl-K9 levels at the promoter region of a subset of genes concomitant with decrease in their expression. Finally, JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation.

Original languageEnglish
Pages (from-to)483-495
Number of pages13
JournalCell
Volume125
Issue number3
DOIs
Publication statusPublished - May 5 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Yamane, K., Toumazou, C., Tsukada, Y. I., Erdjument-Bromage, H., Tempst, P., Wong, J., & Zhang, Y. (2006). JHDM2A, a JmjC-Containing H3K9 Demethylase, Facilitates Transcription Activation by Androgen Receptor. Cell, 125(3), 483-495. https://doi.org/10.1016/j.cell.2006.03.027