通过EZH2破坏B2RNA的稳定性 激活应激反应
Athanasios Zovoilis1, Catherine Cifuentes-Rojas1, Hsueh-Ping Chu1
1Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Cell
|December 17, 2016
概括
聚合蛋白EZH2和B2SINERNA调节压力基因. EZH2在热冲击时触发B2RNA降解,通过RNA聚合酶II激活应激基因. 这揭示了一个新的EZH2功能.
科学领域:
- 表观遗传学
- 分子生物学
- 基因组学
背景情况:
- 超过98%的哺乳动物基因组是非编码的,可转移的元素占该非编码空间的50%.
- 非编码RNA的功能,特别是从可转移的元素,在基因调节是一个活跃的研究领域.
研究的目的:
- 研究EZH2和B2SINERNA在控制应激基因中的作用.
- 阐明EZH2在热应激过程中与B2RNA相互作用的机制.
主要方法:
- 在小鼠细胞中使用热冲击模型.
- 分析了EZH2和B2RNA之间的相互作用.
- 研究了B2RNA对RNA聚合酶II转录延长的影响.
主要成果:
- 证明B2RNA与压力基因结合,抑制它们的转录.
- 显示EZH2在热冲击时被招募,导致B2RNA分裂和随后的压力基因上调.
- 确定B2RNA为RNA聚合酶II的"速度阻塞",热应力释放这种转录制动.
结论:
- 通过B2RNA调节EZH2的新功能,独立于其基因组甲基转移酶活性.
- 调和了EZH2与基因抑制和激活的关联.
- 发现EZH2和B2RNA合作控制涉及热应激反应的大型基因网络.
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