3D Chromosome Regulatory Landscape of Human Pluripotent Cells.
3D Chromosome Regulatory Landscape of Human Pluripotent Cells.
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DOI：
10.1016/j.stem.2015.11.007
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发表时间：
2016-02-04
期刊：
影响因子：
23.9
通讯作者：
Young RA
中科院分区：
文献类型：
--
作者：
Ji X;Dadon DB;Powell BE;Fan ZP;Borges-Rivera D;Shachar S;Weintraub AS;Hnisz D;Pegoraro G;Lee TI;Misteli T;Jaenisch R;Young RA
在这项研究中，我们描述了人类幼稚和启动胚胎干细胞的三维调控染色体结构景观。为了设计这张图，我们确定了这些细胞中的转录增强子和绝缘子，并使用粘着蛋白ChIA-PET数据将它们置于粘着蛋白相关CTCF-CTCF环的背景下。我们发现的CTCF-CTCF环形成了一个由绝缘邻域组成的染色体框架，这些邻域又形成了拓扑相关结构域（TADs），这些结构域在初始状态和启动状态之间的转换过程中基本上被保留下来。增强子-启动子相互作用的调节变化发生在细胞状态转换期间的绝缘邻域内。我们鉴定的CTCF锚区在物种间是保守的，影响基因表达，并且是癌细胞中突变的常见位点，强调了它们在细胞调节中的功能重要性。因此，这些人类多能细胞的3D调控图谱为未来询问染色体结构与发育和疾病中的基因控制之间的关系提供了基础。
In this study, we describe the 3D regulatory chromosome structural landscape of human naive and primed embryonic stem cells. To devise this map, we identified transcriptional enhancers and insulators in these cells and placed them within the context of cohesin-associated CTCF-CTCF loops using cohesin ChIA-PET data. The CTCF-CTCF loops we identified form a chromosomal framework of insulated neighborhoods, which in turn form topologically associated domains (TADs), that are largely preserved during transition between the naïve and primed states. Regulatory changes in enhancer-promoter interactions occur within insulated neighborhoods during cell state transition. The CTCF anchor regions we identified are conserved across species, influence gene expression, and are a frequent site of mutations in cancer cells, underscoring their functional importance in cellular regulation. These 3D regulatory maps of human pluripotent cells therefore provide a foundation for future interrogation of the relationships between chromosome structure and gene control in development and disease.