G9a的动态酸化调节其对染色质可访问性和线粒细胞进展的抑制活性
Qizhi Geng1, Yue-Yu Kong1, Weizhe Li1
1Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Hubei Clinical Research Center of Emergency and Resuscitation, Emergency Center of Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism, RNA Institute, Wuhan University, Wuhan, 430072, China.
线性染色质调节涉及一个
科学领域:
- 细胞生物学 细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 基因组修饰,包括基因组H3在Ser10 (H3S10p) 的酸化和Lys9 (H3K9me) 的甲基化,对于调节线粒染色体结构至关重要.
- 尽管对H3S10p进行了广泛的研究,但在线粒分裂过程中对H3K9me2的动态调节仍然不太了解,H3S10p.
研究的目的:
- 阐明H3K9me2在线粒分裂过程中被动态调节的机制.
- 研究Plk1激酶和PPP2CB酸酶在调节G9a/EHMT2活动中的作用.
- 了解拟议的"基切换"对线粒细胞进展的贡献.
主要方法:
- 使用生物化学测试研究了Plk1和G9a/EHMT2之间的相互作用.
- 使用了G9a/EHMT2.2的模性 (T1045E) 和非可的突变物.
- 在表达G9a/EHMT2突变的细胞中评估了H3K9me2水平,染色质可访问性和线性进展.
- 研究了PPP2CB在Thr1045.5处去化G9a/EHMT2中的作用.
主要成果:
- 在早期线粒分裂期间,plk1激酶酸化G9a/EHMT2在Thr1045 (pT1045),减弱其H3K9me2甲基转移酶活性.
- 具有型G9a突变 (T1045E) 的细胞表现出减少的H3K9me2,增加的染色质可访问性和延迟的线粒分裂.
- 晚期线粒分裂期间PPP2CB对pT1045的脱化会重新激活G9a,增加H3K9me2水平,并与降低的H3S10p相关.
结论:
- "甲基开关"涉及Plk1和PPP2CB对G9a/EHMT2活性进行动态调节,这对于适当的线粒染色体组织至关重要.
- G9a/EHMT2的Plk1-介导的酸化减弱了其在早期线索分裂中的活性,而PPP2CB-介导的脱酸化则在晚期线索分裂中重新激活了它.
- 这种动态调节对于控制H3K9me2水平,染色质可访问性和及时的线粒细胞进展至关重要.
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