| First Author | Sakurai N | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 11962 |
| PubMed ID | 28931940 | Mgi Jnum | J:256540 |
| Mgi Id | MGI:6109720 | Doi | 10.1038/s41598-017-12342-2 |
| Citation | Sakurai N, et al. (2017) BRD4 regulates adiponectin gene induction by recruiting the P-TEFb complex to the transcribed region of the gene. Sci Rep 7(1):11962 |
| abstractText | 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. |
