title: JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis.
abstract: Histone 3 lysine 9 (H3K9) demethylase JMJD1A regulates β-adrenergic-induced systemic metabolism and body weight control. Here we show that JMJD1A is phosphorylated at S265 by protein kinase A (PKA), and this is pivotal to activate the β1-adrenergic receptor gene (Adrb1) and downstream targets including Ucp1 in brown adipocytes (BATs). Phosphorylation of JMJD1A by PKA increases its interaction with the SWI/SNF nucleosome remodelling complex and DNA-bound PPARγ. This complex confers β-adrenergic-induced rapid JMJD1A recruitment to target sites and facilitates long-range chromatin interactions and target gene activation. This rapid gene induction is dependent on S265 phosphorylation but not on demethylation activity. Our results show that JMJD1A has two important roles in regulating hormone-stimulated chromatin dynamics that modulate thermogenesis in BATs. In one role, JMJD1A is recruited to target sites and functions as a cAMP-responsive scaffold that facilitates long-range chromatin interactions, and in the second role, JMJD1A demethylates H3K9 di-methylation.
authors.affiliation: Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Abe
authors.affiliation: 1] Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan [2] Department of Cardiology and Vascular Medicine, Faculty of Medicine, Gadjah Mada University, Yogyakarta 55281, Indonesia.
authors.forename: Royhan
authors.initials: R
authors.lastname: Rozqie
authors.affiliation: Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsumura
authors.affiliation: 1] Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan [2] The Translational Systems Biology and Medicine Initiative, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawamura
authors.affiliation: Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakaki
authors.affiliation: Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Tsurutani
authors.affiliation: Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tanimura-Inagaki
authors.affiliation: Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shiono
authors.affiliation: 1] Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan [2] The Translational Systems Biology and Medicine Initiative, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Magoori
authors.affiliation: Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Ogi
authors.affiliation: UCSF Diabetes Center, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, California 94143-0669, USA.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kajimura
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: 1] Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan [2] Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan [3] The Translational Systems Biology and Medicine Initiative, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Toshiya
authors.identifier: 0000000312247898
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Science, Tokyo 192-0392, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Fukami
authors.affiliation: Metabolic Disease Program, Sanford-Burnham Medical Research Institute, Orlando, Florida 32827, USA.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Osborne
authors.affiliation: Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.affiliation: 1] The Translational Systems Biology and Medicine Initiative, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan [2] Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.affiliation: 1] Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan [2] The Translational Systems Biology and Medicine Initiative, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inagaki
authors.affiliation: 1] Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan [2] The Translational Systems Biology and Medicine Initiative, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Juro
authors.initials: J
authors.lastname: Sakai
mesh_terms: D041721:3T3-L1 Cells; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation; D016678:Genome; D006367:HeLa Cells; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism; D022722:Thermogenesis / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C547788:Adrb1 protein, mouse; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D047495:PPAR gamma; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D010768:Phosphoserine; D056484:Jumonji Domain-Containing Histone Demethylases; C530247:KDM3A protein, human; C511045:Kdm3a protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases