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Nat Commun. 2015 May 7;6:7052. doi: 10.1038/ncomms8052.

JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis.

Author information

1
Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
2
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.
3
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.
4
Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
5
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.
6
UCSF Diabetes Center, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, California 94143-0669, USA.
7
Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
8
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.
9
Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Science, Tokyo 192-0392, Japan.
10
Metabolic Disease Program, Sanford-Burnham Medical Research Institute, Orlando, Florida 32827, USA.
11
Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
12
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.

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.

PMID:
25948511
PMCID:
PMC4432656
DOI:
10.1038/ncomms8052
[Indexed for MEDLINE]
Free PMC Article
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