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bioRxiv · 10.1101/2022.06.01.494329

Hi-TrAC reveals fine-scale chromatin structures organized by transcription factors

Liu, S.·Cao, Y.·Cui, K.·Tang, Q.·Zhao, K.
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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 accessible regulatory elements. Hi-TrAC detects chromatin looping among accessible chromatin regions at single nucleosome resolution. With almost half-million identified loops, we constructed a comprehensive interaction network of regulatory elements across the genome. After integrating chromatin binding profiles of transcription factors, we discovered 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 developed a new methodology to identify a delicate and comprehensive network of cis-regulatory elements, revealing the complexity and a division of labor of TFs in chromatin looping for genome organization and gene expression.

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Liu, S., Cao, Y., Cui, K., Tang, Q., Zhao, K.. 2022-06-03. Hi-TrAC reveals fine-scale chromatin structures organized by transcription factors. https://doi.org/10.1101/2022.06.01.494329

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