Histone demethylase JMJD1A coordinates acute and chronic adaptation to cold stress via thermogenic phospho-switch.
Histone demethylase JMJD1A coordinates acute and chronic adaptation to cold stress via thermogenic phospho-switch.
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DOI：
10.1038/s41467-018-03868-8
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发表时间：
2018-04-19
影响因子：
16.6
通讯作者：
Sakai J
中科院分区：
文献类型：
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作者：
Abe Y;Fujiwara Y;Takahashi H;Matsumura Y;Sawada T;Jiang S;Nakaki R;Uchida A;Nagao N;Naito M;Kajimura S;Kimura H;Osborne TF;Aburatani H;Kodama T;Inagaki T;Sakai J
在哺乳动物的急性冷应激中，组蛋白H3赖氨酸9(H3K9)去甲基酶JMJD1a通过棕色脂肪组织(BAT)的β肾上腺素能信号上调致热基因的表达。除了蝙蝠驱动的产热作用外，哺乳动物还有另一种机制来应对长期的冷应激，方法是诱导皮下白色脂肪组织(ScWAT)变棕色。在这里，我们证明这是一个两步过程，需要β肾上腺素能依赖的S265的磷酸化和JMJD1a对H3K9me2的去甲基化。BAT中组蛋白去甲基化依赖的急性Ucp1诱导和米色scWAT中依赖去甲基化的慢性Ucp1表达为确保急性和慢性适应冷应激之间的有序转换提供了互补的分子机制。JMJD1A通过β-PPARγ-P-JMJD1A复合体介导两条主要的信号通路，即γ-肾上腺素能受体和过氧化物酶体增殖物激活受体-γ激活。JMJD1A的S265磷酸化和随后的H3K9me2的去甲基化可能被证明是通过促进米色脂肪生成而治疗代谢紊乱的一个新的分子靶点。JMJD1A在棕色脂肪组织中是致热基因诱导所必需的。在这里，作者证明白色脂肪组织褐化既需要β肾上腺素能依赖的S265的磷酸化，也需要JMJD1a的去甲基化，而棕色脂肪组织驱动的产热需要β肾上腺素能依赖的S265的磷酸化，但不依赖于H3K9me2的去甲基化。
In acute cold stress in mammals, JMJD1A, a histone H3 lysine 9 (H3K9) demethylase, upregulates thermogenic gene expressions through β-adrenergic signaling in brown adipose tissue (BAT). Aside BAT-driven thermogenesis, mammals have another mechanism to cope with long-term cold stress by inducing the browning of the subcutaneous white adipose tissue (scWAT). Here, we show that this occurs through a two-step process that requires both β-adrenergic-dependent phosphorylation of S265 and demethylation of H3K9me2 by JMJD1A. The histone demethylation-independent acute Ucp1 induction in BAT and demethylation-dependent chronic Ucp1 expression in beige scWAT provides complementary molecular mechanisms to ensure an ordered transition between acute and chronic adaptation to cold stress. JMJD1A mediates two major signaling pathways, namely, β-adrenergic receptor and peroxisome proliferator-activated receptor-γ (PPARγ) activation, via PRDM16-PPARγ-P-JMJD1A complex for beige adipogenesis. S265 phosphorylation of JMJD1A, and the following demethylation of H3K9me2 might prove to be a novel molecular target for the treatment of metabolic disorders, via promoting beige adipogenesis. JMJD1A is essential for thermogenic gene induction in brown adipose tissue. Here the authors show that white adipose tissue beige-ing requires both β-adrenergic-dependent phosphorylation of S265 and demethylation activity of JMJD1A while brown adipose tissue-driven thermogenesis requires β-adrenergic dependent phosphorylation of S265 but is independent of H3K9me2 demethylation.
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影响因子：
4.3
作者：
Manke T;Roider HG;Vingron M
通讯作者：
Vingron M
影响因子：
29
作者：
Kajimura S;Spiegelman BM;Seale P
通讯作者：
Seale P
在单细胞水平上表观遗传调节的动力学。
DOI：
10.1126/science.aab2956
发表时间：
2016-02-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bintu L;Yong J;Antebi YE;McCue K;Kazuki Y;Uno N;Oshimura M;Elowitz MB
通讯作者：
Elowitz MB
影响因子：
16.6
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
通讯作者：
Sakai, Juro
DOI：
10.1038/nrm3072
发表时间：
2011-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
通讯作者：
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