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在ES细胞中染色体重塑剂的全基因组核细胞特异性和功能
Maud de Dieuleveult1, Kuangyu Yen2,3, Isabelle Hmitou1
1Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
Nature
|January 28, 2016
概括
依赖ATP的染色体重塑剂通过向小鼠胚胎干细胞中的特定核细胞来调节转录. 这些重塑剂在活跃和双价基因中起着不同的作用,影响染色体的可访问性和基因表达程序.
科学领域:
- 分子生物学
- 遗传学
- 表观遗传学
背景情况:
- 依赖ATP的染色体重塑剂对于转录中的DNA可访问性至关重要.
- 哺乳动物染色体重塑剂的特定核细胞向和调节作用在很大程度上仍未被描述.
研究的目的:
- 在小鼠胚胎干细胞中绘制八种关键染色体重塑剂的全基因组重塑剂-核细胞相互作用.
- 阐明染色体重塑剂在特定核体中调节转录的机制.
主要方法:
- 使用ChIP-seq进行全基因组的重塑器-核酶相互作用分析.
- 微球菌核酶 (MNase) 消化以定义无核体区域 (NFR).
- 在重建器耗尽后进行转录组分析 (RNA-seq).
主要成果:
- 染色体重塑剂与侧面NFR结合,影响分离转录.
- 富含CpG的NFR含有基因组变体 (H3.3,H2A.Z) 和活性标记 (H3K4me3,H3K27ac).
- 改造器枯竭揭示了取决于环境的作用:积极/消极的活性基因和对立的双价基因.
结论:
- 哺乳动物染色体重塑剂在NFR边缘准特定的核细胞.
- 重塑者在胚胎干细胞中差异调节活跃和双价基因.
- 这些相互作用对维持ES细胞转录程序至关重要.
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