生物
生物素化
染色质
嘉雅宠物
增强子
染色体构象捕获
计算生物学
基因座(遗传学)
支架/基质附着区域
基因
二价染色质
遗传学
转录因子
染色质重塑
分子生物学
作者
Xin Liu,Yuannyu Zhang,Yong Chen,Mushan Li,Feng Zhou,Kailong Li,Hui Cao,Min Ni,Zhimin Gu,Kathryn E. Dickerson,Shiqi Xie,Gary C. Hon,Zhenyu Xuan,Michael Q. Zhang,Zongshu Shao,Jian Xu
出处
期刊:Cell
[Elsevier]
日期:2017-08-01
卷期号:170 (5): 1028-1043.e19
被引量:229
标识
DOI:10.1016/j.cell.2017.08.003
摘要
Cis-regulatory elements (CREs) are commonly recognized by correlative chromatin features, yet the molecular composition of the vast majority of CREs in chromatin remains unknown. Here, we describe a CRISPR affinity purification in situ of regulatory elements (CAPTURE) approach to unbiasedly identify locus-specific chromatin-regulating protein complexes and long-range DNA interactions. Using an in vivo biotinylated nuclease-deficient Cas9 protein and sequence-specific guide RNAs, we show high-resolution and selective isolation of chromatin interactions at a single-copy genomic locus. Purification of human telomeres using CAPTURE identifies known and new telomeric factors. In situ capture of individual constituents of the enhancer cluster controlling human β-globin genes establishes evidence for composition-based hierarchical organization. Furthermore, unbiased analysis of chromatin interactions at disease-associated cis-elements and developmentally regulated super-enhancers reveals spatial features that causally control gene transcription. Thus, comprehensive and unbiased analysis of locus-specific regulatory composition provides mechanistic insight into genome structure and function in development and disease.
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