title: Jmjd3-Mediated H3K27me3 Dynamics Orchestrate Brown Fat Development and Regulate White Fat Plasticity.
abstract: Progression from brown preadipocytes to adipocytes engages two transcriptional programs: the expression of adipogenic genes common to both brown fat (BAT) and white fat (WAT), and the expression of BAT-selective genes. However, the dynamics of chromatin states and epigenetic enzymes involved remain poorly understood. Here we show that BAT development is selectively marked and guided by repressive H3K27me3 and is executed by its demethylase Jmjd3. We find that a significant subset of BAT-selective genes, but not common fat genes or WAT-selective genes, are demarcated by H3K27me3 in both brown and white preadipocytes. Jmjd3-catalyzed removal of H3K27me3, in part through Rreb1-mediated recruitment, is required for expression of BAT-selective genes and for development of beige adipocytes both in vitro and in vivo. Moreover, gain- and loss-of-function Jmjd3 transgenic mice show age-dependent body weight reduction and cold intolerance, respectively. Together, we identify an epigenetic mechanism governing BAT fate determination and WAT plasticity.
authors.affiliation: Department of Molecular, Cell and Cancer Biology and Program in Molecular Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Dongning
authors.initials: D
authors.lastname: Pan
authors.affiliation: Department of Molecular, Cell and Cancer Biology and Program in Molecular Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Molecular, Cell and Cancer Biology and Program in Molecular Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Lihua J
authors.initials: LJ
authors.lastname: Zhu
authors.affiliation: Department of Molecular, Cell and Cancer Biology and Program in Molecular Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Tie
authors.initials: T
authors.lastname: Zou
authors.affiliation: Department of Molecular, Cell and Cancer Biology and Program in Molecular Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Ou
authors.affiliation: Department of Molecular, Cell and Cancer Biology and Program in Molecular Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
authors.forename: William
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Molecular, Cell and Cancer Biology and Program in Molecular Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA. Electronic address: yongxu.wang@umassmed.edu.
authors.forename: Yong-Xu
authors.initials: YX
authors.lastname: Wang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000196:embryology*; D052436:Adipose Tissue, White / Q000196:embryology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001835:Body Weight; D004268:DNA-Binding Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007473:Ion Channels / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D017423:Sequence Analysis, RNA; D022722:Thermogenesis / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D019076:Transgenes; D000071256:Uncoupling Protein 1
chemical_list: D051017:Apoptosis Regulatory Proteins; C112510:Cidea protein, mouse; D004268:DNA-Binding Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000606556:Rreb1 protein, mouse; D014157:Transcription Factors; D000071256:Uncoupling Protein 1; D056484:Jumonji Domain-Containing Histone Demethylases; C523761:Kdm6b protein, mouse