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한빛사논문
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Proc. Natl. Acad. Sci. USA, Nov 07 2023, 120 (45) | https://doi.org/10.1073/pnas.2313285120
Ultrafine mapping of chromosome conformation at hundred basepair resolution reveals regulatory genome architecture
Yizhou Zhua,1, Michael G. Rosenfeldb,c,1, and Yousin Suha,c,1
aDepartment of Obstetrics and Gynecology, Columbia University, New York, NY 10032;
bDepartment of Medicine, University of California San Diego, La Jolla, CA 92093;
cDepartment of Genetics and Development, Columbia University, New York, NY 10032
1To whom correspondence may be addressed. : Yizhou Zhu, Michael G. Rosenfeld, Yousin Suh
Abstract
The resolution limit of chromatin conformation capture methodologies (3Cs) has restrained their application in detection of fine-level chromatin structure mediated by cis-regulatory elements (CREs). Here, we report two 3C-derived methods, Tri-4C and Tri-HiC, which utilize multirestriction enzyme digestions for ultrafine mapping of targeted and genome-wide chromatin interaction, respectively, at up to one hundred basepair resolution. Tri-4C identified CRE loop interaction networks and quantitatively revealed their alterations underlying dynamic gene control. Tri-HiC uncovered global fine-gauge regulatory interaction networks, identifying >20-fold more enhancer:promoter (E:P) loops than in situ Hi-C. In addition to vastly improved identification of subkilobase-sized E:P loops, Tri-HiC also uncovered interaction stripes and contact domain insulation from promoters and enhancers, revealing their loop extrusion behaviors resembling the topologically associating domain boundaries. Tri-4C and Tri-HiC provide robust approaches to achieve the high-resolution interactome maps required for characterizing fine-gauge regulatory chromatin interactions in analysis of development, homeostasis, and disease.
논문정보
- Research article
- 2023년 11월 (BRIC 등록일 2023-11-09)
- 국외 연구진
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