作为核细胞酸补丁的守门人,ubiquitinated histone H2B 作为核细胞酸补丁的守门人
Chad W Hicks1, Sanim Rahman1, Susan L Gloor2
1Department of Biophysics & Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Nucleic acids research
|August 16, 2024
概括
基因基因的无处不在调节了基因活动. 与H2AK119ub不同的是,H2BK120的单双化阻断了蛋白质与核细胞酸补丁的结合,揭示了它在染色质调节中的独特作用.
科学领域:
- 表观遗传学和染色体生物学
- 分子和结构生物学分子和结构生物学.
- 基因调节 基因调节
背景情况:
- 基因组无化,特别是H2BK120ub和H2AK119ub,在基因转录和染色质结构中起着关键但相反的作用.
- H2BK120ub与活性尤克罗马丁相关,而H2AK119ub标志着抑制的异性染色素.
- 虽然已知H2BK120ub对蛋白质结合的影响,但它干扰酸性贴片相互作用的机制尚不清楚.
研究的目的:
- 阐明H2BK120ub和H2AK119ub如何差异调节蛋白质与核细胞酸性补丁结合的结构基础.
- 为了研究H2BK120ub遮住酸性斑块的机制.
主要方法:
- 低温电子显微镜 (cryoEM) 用于确定H2BK120ub和H2AK119ub核体的结构.
- 分子动力学 (MD) 模拟以评估无处不在定位的稳定性.
- 生物化学试验测试核细胞与酸性补丁结合蛋白 (RCC1,LANA) 和抗体的核细胞相互作用.
主要成果:
- 低温EM结构显示,H2BK120ub,但不是H2AK119ub,采取了封闭核细胞酸补丁的位置.
- MD模拟证实了H2BK120ub核细胞体中在酸性斑块上的稳定ubiquitin定位.
- H2BK120ub,但不是H2AK119ub,阻止RCC1,LANA和特定抗体与酸性补丁结合.
结论:
- H2BK120ub通过直接封闭,作为核细胞酸补丁的"守门人".
- 基因组H2BK120和H2AK119的无处不在有不同的机制来调节与核细胞的蛋白质相互作用.
- 这些发现提供了对基因调节和染色体组织中基因基因化作用的差异性作用的洞察.
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