TY - JOUR
T1 - JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis
AU - Abe, Yohei
AU - Rozqie, Royhan
AU - Matsumura, Yoshihiro
AU - Kawamura, Takeshi
AU - Nakaki, Ryo
AU - Tsurutani, Yuya
AU - Tanimura-Inagaki, Kyoko
AU - Shiono, Akira
AU - Magoori, Kenta
AU - Nakamura, Kanako
AU - Ogi, Shotaro
AU - Kajimura, Shingo
AU - Kimura, Hiroshi
AU - Tanaka, Toshiya
AU - Fukami, Kiyoko
AU - Osborne, Timothy F.
AU - Kodama, Tatsuhiko
AU - Aburatani, Hiroyuki
AU - Inagaki, Takeshi
AU - Sakai, Juro
N1 - Funding Information:
We thank Dr Mitsuyoshi Nakao for helpful discussion, Dr Tadashi Shiraishi for reading the manuscript, Drs Yoichi Shinkai and Makoto Tachibana for Jmjd1a − / − mice, Noriko Nagao, Aoi Uchida, Saki Kawashima, Reiko Kuwahara, Akashi Taguchi-Izumi and Ayano Yoshida for their technical assistance, and other members of the Sakai laboratory for their helpful discussion. This work was supported in Grant-in-Aid for Scientific Research (S) (grant number 22229009) and (B) (grant number 25291002), the Project for Developing Innovation Systems of MEXT and, in part, by Grants-in-Aid for Scientific Research on Priority Areas (17054004) from the Ministry of Education, Culture, Sports, Science and Technology.
Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/5/7
Y1 - 2015/5/7
N2 - 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 PPAR 3. 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.
AB - 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 PPAR 3. 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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U2 - 10.1038/ncomms8052
DO - 10.1038/ncomms8052
M3 - Article
C2 - 25948511
AN - SCOPUS:84929207487
SN - 2041-1723
VL - 6
JO - Nature Communications
JF - Nature Communications
M1 - 7052
ER -