高分辨率的Xist结合图显示了X染色体失活期间的两步传播
Matthew D Simon1,2, Stefan F Pinter1,3, Rui Fang2
1Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02114.
Nature
|October 29, 2013
概括
基因组长非编码RNA (lncRNA) 通过覆盖不活跃的X染色体来引导X染色体失活 (XCI). 囊扩散在初始XCI期间遵循两步机制,但在维护期间迅速覆盖了基因丰富和基因贫穷的区域.
科学领域:
- 遗传学 是一个遗传学.
- 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:
- 在哺乳动物中,X染色体不活化 (XCI) 均等化了两性基因剂量.
- Xist长非编码RNA (lncRNA) 对于启动和维持XCI至关重要.
- 在X染色体中扩散Xist的机制仍然不完全理解.
研究的目的:
- 在XCI期间调查Xist的高分辨率结合模式.
- 阐明Xist传播的时空动态及其与表观遗传修饰物的关系.
- 了解染色质状态在Xist介导沉默中的作用.
主要方法:
- 通过杂交捕获的染色体可访问性,然后进行测序 (CHART-seq) 用于绘制Xist结合的地图.
- 在 de novo XCI 期间,在整个发育时间过程中分析了结结.
- 囊局部与多孔镇压复合体2 (PRC2) 和H3K27me3标记相关.
主要成果:
- 囊结合遵循两步机制:最初准基因丰富的岛屿,然后扩散到基因贫穷的领域.
- 囊结合与PRC2密度和H3K27me3成正比,这表明共迁移.
- 在急性切除后的几个小时内,Xist迅速重新覆盖非活性X染色体,表明了原始染色体状态.
结论:
- 在XCI的建立和维护过程中,石的扩散表现出明显的特定阶段的机制.
- 不活跃的X染色体具有原始染色体状态,这有助于快速恢复Xist.
- 这些发现为Xist.对X染色体失活的动态调节提供了新的见解.
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