title: Epigenetic regulation of adipogenesis by PHF2 histone demethylase.
abstract: PHF2 is a JmjC family histone demethylase that removes the methyl group from H3K9me2 and works as a coactivator for several metabolism-related transcription factors. In this study, we examined the in vivo role of PHF2 in mice. We generated Phf2 floxed mice, systemic Phf2 null mice by crossing Phf2 floxed mice with CMV-Cre transgenic mice, and tamoxifen-inducible Phf2 knockout mice by crossing Phf2 floxed mice with Cre-ERT2 transgenic mice. Systemic Phf2 null mice had partial neonatal death and growth retardation and exhibited less adipose tissue and reduced adipocyte numbers compared with control littermates. Tamoxifen-induced conditional knockout of PHF2 resulted in impaired adipogenesis in stromal vascular cells from the adipose tissue of tamoxifen-inducible Phf2 knockout mice as well as of Phf2 knocked-down 3T3-L1 cells. PHF2 interacts with CEBPA and demethylates H3K9me2 in the promoters of CEBPA-regulated adipogenic genes. These findings suggest that PHF2 histone demethylase potentiates adipogenesis through interaction with CEBPA in vivo. Taken together, PHF2 may be a novel therapeutic target in the treatment of obesity and the metabolic syndrome.
authors.affiliation: Laboratory of Epigenetic Skeletal Diseases, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Okuno
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ohtake
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Igarashi
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takada
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Imai
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis; D052436:Adipose Tissue, White / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D015430:Weight Gain
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C530718:CEBPA protein, mouse; D004268:DNA-Binding Proteins; D006657:Histones; D011994:Recombinant Proteins; D056466:Histone Demethylases