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

Authors:
Yohei Abe
Yohei Abe
Research Center for Advanced Science and Technology (RCAST)
Royhan Rozqie
Royhan Rozqie
Gadjah Mada University
Indonesia
Yoshihiro Matsumura
Yoshihiro Matsumura
Oregon Health and Science University
Takeshi Kawamura
Takeshi Kawamura
Research Center for Advanced Science and Technology
Japan
Ryo Nakaki
Ryo Nakaki
Research Center for Advanced Science and Technology (RCAST)
Yuya Tsurutani
Yuya Tsurutani
Chiba University Graduate School of Medicine
Japan

Nat Commun 2015 May 7;6:7052. Epub 2015 May 7.

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.

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.
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May 2015
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