JHDM2A, a JMJC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor Journal Article
| Authors: | Yamane, K.; Toumazou, C.; Tsukada, Y. I.; Erdjument-Bromage, H.; Tempst, P.; Wong, J.; Zhang, Y. |
| Article Title: | JHDM2A, a JMJC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor |
| 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. © 2006 Elsevier Inc. All rights reserved. |
| Keywords: | protein expression; unclassified drug; promoter region; nonhuman; chemical analysis; animal cell; mouse; animals; mice; gene targeting; embryo; transcription initiation; down-regulation; enzyme activity; hela cells; mutational analysis; cercopithecus aethiops; cos cells; animalia; amino acid sequence; molecular sequence data; histone; iron; base sequence; androgen receptor; protein structure, tertiary; trans-activators; receptors, androgen; catalytic domain; zinc finger protein; histones; enzyme purification; gonadal steroid hormones; enzyme; demethylation; ketoglutaric acids; promoter regions (genetics); trans-activation (genetics); oxidoreductases, n-demethylating; chromatography; enzyme jhdm1; enzyme jhdm2a |
| Journal Title: | Cell |
| Volume: | 125 |
| Issue: | 3 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2006-05-05 |
| Start Page: | 483 |
| End Page: | 495 |
| Language: | English |
| DOI: | 10.1016/j.cell.2006.03.027 |
| PUBMED: | 16603237 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 273" - "Export Date: 4 June 2012" - "CODEN: CELLB" - "Source: Scopus" |
