Hi-TrAC reveals division of labor of transcription factors in organizing chromatin loops

Shuai Liu, Yaqiang Cao, Kairong Cui, Qingsong Tang and Keji Zhao ()
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Shuai Liu: National Institutes of Health
Yaqiang Cao: National Institutes of Health
Kairong Cui: National Institutes of Health
Qingsong Tang: National Institutes of Health
Keji Zhao: National Institutes of Health

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract The three-dimensional genomic structure plays a critical role in gene expression, cellular differentiation, and pathological conditions. It is pivotal to elucidate fine-scale chromatin architectures, especially interactions of regulatory elements, to understand the temporospatial regulation of gene expression. In this study, we report Hi-TrAC as a proximity ligation-free, robust, and sensitive technique to profile genome-wide chromatin interactions at high-resolution among regulatory elements. Hi-TrAC detects chromatin looping among accessible regions at single nucleosome resolution. With almost half-million identified loops, we reveal a comprehensive interaction network of regulatory elements across the genome. After integrating chromatin binding profiles of transcription factors, we discover that cohesin complex and CTCF are responsible for organizing long-range chromatin loops, related to domain formation; whereas ZNF143 and HCFC1 are involved in structuring short-range chromatin loops between regulatory elements, which directly regulate gene expression. Thus, we introduce a methodology to identify a delicate and comprehensive network of cis-regulatory elements, revealing the complexity and a division of labor of transcription factors in organizing chromatin loops for genome organization and gene expression.

Date: 2022
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DOI: 10.1038/s41467-022-34276-8

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