期刊
CELL
卷 170, 期 5, 页码 1028-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2017.08.003
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资金
- NIH [R01MH102616]
- Cecil H. and Ida Green Endowment
- SKRDPC grant [2017YFA0505503]
- NSFC [91519326, 31671384]
- NSFC grant [31670836]
- National Key R&D Program of China [2017YFA0505100]
- Shanghai Institute of Higher Learning [TP2015003]
- 100-Talent'' Program of Chinese Academy of Sciences [Y516C11851]
- NIH grants [K01DK093543, R03DK101665, R01DK111430]
- Cancer Prevention and Research Institute of Texas (CPRIT) New Investigator award [RR140025]
- American Cancer Society award
- Harold C. Simmons Comprehensive Cancer Center at UT Southwestern [IRG-02-196]
- Welch Foundation grant [I-1942-20170325]
- American Society of Hematology Scholar award
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 beta-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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