在心脏发育过程中,CHD4和SMYD1抑制了常见的转录程序
Wei Shi1, Lauren K Wasson2,3, Kerry M Dorr1
1Department of Biology and Genetics, McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC 27599, USA.
概括
染色体调节器CHD4在心脏发育中与SMYD1相互作用. 它们一起抑制了对心脏形态发生至关重要的基因,揭示了CHD4在发育中的心脏中的新角色.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 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:
- 染色体重塑对于发育过程中的基因表达至关重要.
- CHD4蛋白是NuRD复合体的核心,已知可以抑制转录.
- 在心肌细胞中CHD4的功能及其在心脏中的相互作用仍然不清楚.
研究的目的:
- 研究CHD4在心肌细胞功能和心脏发育中的作用.
- 为了确定心脏组织中CHD4的新型蛋白相互作用.
- 阐明CHD4和SMYD1在心脏基因调节中的功能背后的分子机制.
主要方法:
- 定量蛋白质组学用于识别CHD4相互作用伙伴.
- 无胚胎小鼠心脏的转录组分析 (RNA-seq).
- 在零胚胎小鼠心脏中进行染色质可访问性测试 (ATAC-seq).
主要成果:
- 发现CHD4与肌肉特异性基因组甲基转移酶SMYD1相互作用.
- 在胚胎小鼠心脏中失去Smyd1或Chd4导致了常见基因的抑制.
- 这些被抑制的基因参与糖解,缺氧反应和血管生成.
结论:
- 通过与SMYD1.1的相互作用,CHD4在心脏发育中发挥着关键作用.
- SMYD1和CHD4合作抑制关键基因和心脏形态发生过程中必不可少的途径.
- 这项研究揭示了SMYD1在心脏发育过程中抑制心脏转录的新机制.
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