ATRX指导PRC2与XistRNA的结合,并针对Polycomb的目标
Kavitha Sarma1, Catherine Cifuentes-Rojas1, Ayla Ergun2
1Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA USA; Department of Genetics, Harvard Medical School, Boston, MA USA.
Cell
|November 24, 2014
概括
阿尔法-血症X关联智力障碍综合征 (ATRX) 蛋白质结合XistRNA,使得聚合体抑制复合体2 (PRC2) 能够用于X染色体失活 (XCI) 的招募. 失去ATRX会破坏PRC2的全基因组向.
科学领域:
- 表观遗传学和基因调控
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- X染色体不活化 (XCI) 沉默女性的一个X染色体,对于剂量补偿至关重要.
- 长非编码RNAXist和多抑制复合体2 (PRC2) 是XCI介导的转录抑制中的关键参与者.
- PRC2还针对其他基因组位点进行抑制,但其特异性机制尚未完全理解.
研究的目的:
- 用XCI作为模型系统来识别Xist和PRC2功能的新型调节剂.
- 阐明ATRX在XCI和全基因组期间PRC2的招募和功能中的作用.
主要方法:
- 无偏的蛋白质组学方法来分离Xist和PRC2相互作用的蛋白质.
- RNA免疫沉和体内结合测试以确认ATRX-XistRNA相互作用.
- 表观遗传学分析 (例如,ChIP-seq) 以评估ATRX枯竭后的PRC2局部化和基因表达变化.
主要成果:
- ATRX被确定为一种新型,高亲和度的RNA结合蛋白,它与XistRNA直接相互作用.
- ATRX对于PRC2加载到XistRNA及其随后沿X染色体传播至关重要.
- 丢失ATRX导致PRC2的全基因组再分配,导致Polycomb目标基因的脱抑制.
结论:
- 在XCI和其他基因组部位中,ATRX作为PRC2向和功能的关键特异性决定因素.
- 这项研究揭示了ATRX作为一种RNA结合蛋白,对于表观遗传沉默通路至关重要的意想不到的作用.
- 了解ATRX在PRC2招募中的作用,为基因表达和表观遗传情景的调节提供了新的见解.
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