title: PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B.
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.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Baba
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ohtake
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Okuno
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yokota
authors.forename: Maiko
authors.initials: M
authors.lastname: Okada
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Imai
authors.forename: Min
authors.initials: M
authors.lastname: Ni
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Meyer
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Igarashi
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.forename: Myles
authors.initials: M
authors.lastname: Brown
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D056466:Histone Demethylases / Q000737:chemistry / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C503805:ARID5B protein, human; C503806:Arid5b protein, mouse; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C117905:PHF2 protein, human; D014157:Transcription Factors; D056466:Histone Demethylases; D017868:Cyclic AMP-Dependent Protein Kinases