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Histone demethylase JMJD1C is phosphorylated by mTOR to activate de novo lipogenesis.

ABSTRACT: Fatty acid and triglyceride synthesis increases greatly in response to feeding and insulin. This lipogenic induction involves coordinate transcriptional activation of various enzymes in lipogenic pathway, including fatty acid synthase and glycerol-3-phosphate acyltransferase. Here, we show that JMJD1C is a specific histone demethylase for lipogenic gene transcription in liver. In response to feeding/insulin, JMJD1C is phosphorylated at T505 by mTOR complex to allow direct interaction with USF-1 for recruitment to lipogenic promoter regions. Thus, by demethylating H3K9me2, JMJD1C alters chromatin accessibility to allow transcription. Consequently, JMJD1C promotes lipogenesis in vivo to increase hepatic and plasma triglyceride levels, showing its role in metabolic adaption for activation of the lipogenic program in response to feeding/insulin, and its contribution to development of hepatosteatosis resulting in insulin resistance.

SUBMITTER: Viscarra JA

PROVIDER: S-EPMC7005700 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Histone demethylase JMJD1C is phosphorylated by mTOR to activate de novo lipogenesis.

Viscarra Jose A JA Wang Yuhui Y Nguyen Hai P HP Choi Yoon Gi YG Sul Hei Sook HS

Nature communications 20200207 1

Fatty acid and triglyceride synthesis increases greatly in response to feeding and insulin. This lipogenic induction involves coordinate transcriptional activation of various enzymes in lipogenic pathway, including fatty acid synthase and glycerol-3-phosphate acyltransferase. Here, we show that JMJD1C is a specific histone demethylase for lipogenic gene transcription in liver. In response to feeding/insulin, JMJD1C is phosphorylated at T505 by mTOR complex to allow direct interaction with USF-1 ...[more]

PMID: 32034158

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