BRD4 regulates adiponectin gene induction by recruiting the P-TEFb complex to the transcribed region of the gene

被引：26

作者：

Sakurai, Naoko ^{[1
]}

Inamochi, Yuko ^{[1
]}

Inoue, Takuya ^{[2
]}

Hariya, Natsuyo ^{[3
]}

Kawamura, Musashi ^{[4
]}

Yamada, Masami ^{[1
]}

Dey, Anup ^{[5
]}

Nishiyama, Akira ^{[5
]}

Kubota, Takeo ^{[6
]}

Ozato, Keiko ^{[5
]}

Goda, Toshinao ^{[1
]}

Mochizuki, Kazuki ^{[1
,4
]}

机构：

[1] Univ Shizuoka, Grad Sch Nutr & Environm Sci, Lab Nutr Physiol, Shizuoka, Japan

[2] Univ Yamanashi, Interdisciplinary Grad Sch Med & Engn, Div Engn, Yamanashi, Japan

[3] Yamanashi Gakuin Univ, Fac Hlth & Nutr, Dept Nutr, Yamanashi, Japan

[4] Univ Yamanashi, Fac Life & Environm Sci, Dept Local Prod & Food Sci, Lab Food & Nutr Sci, Yamanashi, Japan

[5] NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD USA

[6] Seitoku Univ, Fac Child Studies, Dept Child Studies, Chiba, Japan

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

ACTIVATED-RECEPTOR-GAMMA; BROMODOMAIN PROTEIN BRD4; BINDING PROTEIN; EXPRESSION; ADIPOSE; OBESITY; DIFFERENTIATION; ADIPOCYTES; CHREBP;

D O I：

10.1038/s41598-017-12342-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We previously reported that induction of the adipocyte-specific gene adiponectin (Adipoq) during 3T3-L1 adipocyte differentiation is closely associated with epigenetic memory histone H3 acetylation on the transcribed region of the gene. We used 3T3-L1 adipocytes and Brd4 heterozygous mice to investigate whether the induction of Adipoq during adipocyte differentiation is regulated by histone acetylation and the binding protein bromodomain containing 4 (BRD4) on the transcribed region. Depletion of BRD4 by shRNA and inhibition by (+)-JQ1, an inhibitor of BET family proteins including BRD4, reduced Adipoq expression and lipid droplet accumulation in 3T3-L1 adipocytes. Additionally, the depletion and inhibition of BRD4 reduced the expression of many insulin sensitivity-related genes, including genes related to lipid droplet accumulation in adipocytes. BRD4 depletion reduced P-TEFb recruitment and histone acetylation on the transcribed region of the Adipoq gene. The expression levels of Adipoq and fatty acid synthesis-related genes and the circulating ADIPOQ protein level were lower in Brd4 heterozygous mice than in wild-type mice at 21 days after birth. These findings indicate that BRD4 regulates the Adipoq gene by recruiting P-TEFb onto acetylated histones in the transcribed region of the gene and regulates adipocyte differentiation by regulating the expression of genes related to insulin sensitivity.

引用

页数：12