JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis.
JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis.
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DOI：
10.1038/ncomms8052
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发表时间：
2015-05-07
影响因子：
16.6
通讯作者：
Sakai, Juro
中科院分区：
文献类型：
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作者：
Abe, Yohei;Rozqie, Royhan;Matsumura, Yoshihiro;Kawamura, Takeshi;Nakaki, Ryo;Tsurutani, Yuya;Tanimura-Inagaki, Kyoko;Shiono, Akira;Magoori, Kenta;Nakamura, Kanako;Ogi, Shotaro;Kajimura, Shingo;Kimura, Hiroshi;Tanaka, Toshiya;Fukami, Kiyoko;Osborne, Timothy F.;Kodama, Tatsuhiko;Aburatani, Hiroyuki;Inagaki, Takeshi;Sakai, Juro
组蛋白3赖氨酸9（H3 K9）脱甲基酶JMJD 1A调节β-肾上腺素能诱导的全身代谢和体重控制。在这里，我们发现JMJD 1A在S265处被蛋白激酶A（PKA）磷酸化，这对于激活棕色脂肪细胞（BAT）中的β1-肾上腺素能受体基因（Adrb 1）和下游靶点包括Ucp 1至关重要。PKA对JMJD 1A的磷酸化增加了其与SWI/SNF核小体重塑复合物和DNA结合的PPARγ的相互作用。该复合物使β-肾上腺素能诱导的JMJD 1A快速募集到靶位点，并促进长距离染色质相互作用和靶基因激活。这种快速的基因诱导依赖于S265磷酸化，但不依赖于去甲基化活性。我们的研究结果表明，JMJD 1A有两个重要的作用，在调节染色质动力学，调节BAT的产热。在一个作用中，JMJD 1A被募集到靶位点，并作为cAMP响应性支架发挥作用，促进长距离染色质相互作用，在第二个作用中，JMJD 1A使H3 K9去甲基化。 去甲基酶JMJD 1A激活产热相关靶基因以响应β-肾上腺素能激素。在这里，作者表明JMJD 1A在S265处的磷酸化增加了其与SWI/SNF染色质重塑剂的相互作用，导致长距离染色质相互作用和靶基因激活。
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. Demethylase JMJD1A activates thermogenesis-related target genes in response to β-adrenergic hormones. Here, the authors show that phosphorylation of JMJD1A at S265 increases its interaction with the SWI/SNF chromatin remodeler, leading to long-range chromatin interactions and target gene activation.
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DOI：
10.1038/nrm3072
发表时间：
2011-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1074/jbc.m110.154732
发表时间：
2011-01-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Daigo K;Kawamura T;Ohta Y;Ohashi R;Katayose S;Tanaka T;Aburatani H;Naito M;Kodama T;Ihara S;Hamakubo T
通讯作者：
Hamakubo T
影响因子：
1.2
作者：
Aune, Ulrike Liisberg;Ruiz, Lauren;Kajimura, Shingo
通讯作者：
Kajimura, Shingo
影响因子：
64.8
作者：
Okada, Yuki;Scott, Greg;Zhang, Yi
通讯作者：
Zhang, Yi
影响因子：
4.8
作者：
Liang, GS;Yang, J;Brown, MS
通讯作者：
Brown, MS