PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B

被引:146
作者
Baba, Atsushi [1 ]
Ohtake, Fumiaki [1 ,2 ]
Okuno, Yosuke [1 ,2 ]
Yokota, Kenichi [1 ]
Okada, Maiko [1 ,2 ]
Imai, Yuuki [1 ,3 ,4 ]
Ni, Min [3 ,4 ]
Meyer, Clifford A. [5 ,6 ]
Igarashi, Katsuhide [7 ]
Kanno, Jun [7 ]
Brown, Myles [3 ,4 ]
Kato, Shigeaki [1 ,2 ]
机构
[1] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan
[2] Japan Sci & Technol Agcy, ERATO, Kawaguchishi, Saitama 3320012, Japan
[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Boston, MA 02115 USA
[5] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA
[6] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA
[7] Natl Inst Hlth Sci, Div Cellular & Mol Toxicol, Setagaya Ku, Tokyo 1588501, Japan
关键词
DOMAIN-CONTAINING PROTEINS; HEPATIC GLUCONEOGENESIS; CHROMATIN MODIFICATIONS; GLUCOSE-METABOLISM; NUCLEAR RECEPTORS; DIOXIN RECEPTOR; TRANSCRIPTION; COACTIVATOR; FAMILY; PGC-1;
D O I
10.1038/ncb2228
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Reversible histone methylation and demethylation are highly regulated processes that are crucial for chromatin reorganization and regulation of gene transcription in response to extracellular conditions. However, the mechanisms that regulate histone-modifying enzymes are largely unknown. Here, we characterized a protein kinase A (PKA)-dependent histone lysine demethylase complex, PHF2-ARID5B. PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. We found that phosphorylated PHF2 then associates with ARID5B, a DNA-binding protein, and induce demethylation of methylated ARID5B. This modification leads to targeting of the PHF2 ARID5B complex to its target promoters, where it removes the repressive H3K9Me2 mark. These findings suggest that the PHF2 ARID5B complex is a signal-sensing modulator of histone methylation and gene transcription, in which phosphorylation of PHF2 enables subsequent formation of a competent and specific histone demethylase complex.
引用
收藏
页码:668 / U101
页数:23
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