Department of Nutritional Science and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Mol Cell. 2013 Jan 24;49(2):283-97. doi: 10.1016/j.molcel.2012.10.028. Epub 2012 Dec 6.
Fatty acid and triglyceride synthesis is induced in response to feeding and insulin. This lipogenic induction involves coordinate transcriptional activation of lipogenic enzymes, including fatty acid synthase and glycerol-3-phosphate acyltransferase. We recently reported the importance of USF-1 phosphorylation and subsequent acetylation in insulin-induced lipogenic gene activation. Here, we show that Brg1/Brm-associated factor (BAF) 60c is a specific chromatin remodeling component for lipogenic gene transcription in liver. In response to insulin, BAF60c is phosphorylated at S247 by atypical PKCζ/λ, which causes translocation of BAF60c to the nucleus and allows a direct interaction of BAF60c with USF-1 that is phosphorylated by DNA-PK and acetylated by P/CAF. Thus, BAF60c is recruited to form the lipoBAF complex to remodel chromatin structure and to activate lipogenic genes. Consequently, BAF60c promotes lipogenesis in vivo and increases triglyceride levels, demonstrating its role in metabolic adaption to activate the lipogenic program in response to feeding and insulin.
脂肪酸和甘油三酯的合成是对进食和胰岛素的反应而诱导的。这种生脂诱导涉及生脂酶的协调转录激活，包括脂肪酸合酶和甘油-3-磷酸酰基转移酶。我们最近报道了 USF-1 磷酸化和随后的乙酰化在胰岛素诱导的生脂基因激活中的重要性。在这里，我们表明 Brg1/Brm 相关因子 (BAF) 60c 是肝脏中脂生成基因转录的特定染色质重塑成分。对胰岛素的反应，BAF60c 在 S247 处被非典型 PKCζ/λ 磷酸化，导致 BAF60c 易位到细胞核，并允许 BAF60c 与 USF-1 的直接相互作用，该 USF-1 由 DNA-PK 磷酸化和 P/CAF 乙酰化。因此，BAF60c 被募集形成 lipoBAF 复合物以重塑染色质结构并激活生脂基因。因此，BAF60c 在体内促进脂肪生成并增加甘油三酯水平，表明其在代谢适应中的作用，以响应进食和胰岛素激活生脂程序。
