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

Atsushi Baba, Fumiaki Ohtake, Yosuke Okuno, Kenichi Yokota, Maiko Okada, Yuuki Imai, Min Ni, Clifford A. Meyer, Katsuhide Igarashi, Jun Kanno, Myles Brown, Shigeaki Kato

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)668-675
Number of pages8
JournalNature Cell Biology
Volume13
Issue number6
DOIs
Publication statusPublished - 2011 Jun
Externally publishedYes

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Histone Demethylases
Cyclic AMP-Dependent Protein Kinases
Histones
Methylation
Phosphorylation
DNA-Binding Proteins
Genes
Chromatin
Enzymes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Baba, A., Ohtake, F., Okuno, Y., Yokota, K., Okada, M., Imai, Y., ... Kato, S. (2011). PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B. Nature Cell Biology, 13(6), 668-675. https://doi.org/10.1038/ncb2228

PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B. / Baba, Atsushi; Ohtake, Fumiaki; Okuno, Yosuke; Yokota, Kenichi; Okada, Maiko; Imai, Yuuki; Ni, Min; Meyer, Clifford A.; Igarashi, Katsuhide; Kanno, Jun; Brown, Myles; Kato, Shigeaki.

In: Nature Cell Biology, Vol. 13, No. 6, 06.2011, p. 668-675.

Research output: Contribution to journalArticle

Baba, A, Ohtake, F, Okuno, Y, Yokota, K, Okada, M, Imai, Y, Ni, M, Meyer, CA, Igarashi, K, Kanno, J, Brown, M & Kato, S 2011, 'PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B', Nature Cell Biology, vol. 13, no. 6, pp. 668-675. https://doi.org/10.1038/ncb2228
Baba, Atsushi ; Ohtake, Fumiaki ; Okuno, Yosuke ; Yokota, Kenichi ; Okada, Maiko ; Imai, Yuuki ; Ni, Min ; Meyer, Clifford A. ; Igarashi, Katsuhide ; Kanno, Jun ; Brown, Myles ; Kato, Shigeaki. / PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B. In: Nature Cell Biology. 2011 ; Vol. 13, No. 6. pp. 668-675.
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