Brg1对染色质的调节是心肌发育和疾病的基础
Calvin T Hang1, Jin Yang, Pei Han
1Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature
|July 3, 2010
概括
Brg1是一种染色质重塑剂,维持心肌细胞在胚胎状态. 在心脏应激期间Brg1的重新激活会导致病态基因转移,导致心脏缩和衰竭.
科学领域:
- 分子生物学分子生物学
- 心血管研究的心血管研究.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 心脏缩和衰竭涉及基因表达的变化.
- 成年心肌细胞表达阿尔法-肌酸重链 (MHC),而胚胎细胞表达β-MHC.
- 心脏压力诱导成人心脏从α-MHC转变为β-MHC.
研究的目的:
- 研究Brg1在调节心脏生长,分化和基因表达中的作用.
- 阐明Brg1控制心肌细胞发育和病理基因表达的表观遗传机制.
主要方法:
- 研究了Brg1在胚胎和成年小鼠心肌细胞中的功能.
- 研究了 Brg1 与基因组脱乙酶 (HDAC) 和多 (ADP 核糖) 聚合酶 (PARP) 的相互作用.
- 在患有多变性心肌病的患者中分析了Brg1表达.
主要成果:
- 在胚胎中,Brg1促进肌细胞增殖,并通过调节MHC表达来维持胎儿心脏分化.
- 在成年人中,Brg1被压力重新激活,与HDAC和PARP形成复合体,以诱导α-MHC转变为β-MHC.
- 防止Brg1重新表达减少了心脏缩,并逆转了MHC开关.
- 过高的BRG1水平与高性心肌病患者的疾病严重程度相关.
结论:
- Brg1在保持心肌细胞在胚胎状态方面发挥着至关重要的作用.
- Brg1,HDAC和PARP通过表观遗传机制合作,在发育和疾病期间控制心脏基因表达.
- 准Brg1再表达可能为心脏缩和心脏衰竭提供治疗潜力.
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