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

• Published in: Nature communications 2022-11, Vol.13 (1), p.6679-6679, Article 6679
• Main Authors: Liu, Shuai, Cao, Yaqiang, Cui, Kairong, Tang, Qingsong, Zhao, Keji
• Format: Article
• Language: English
• Subjects: 38/15; 38/39; 631/1647/2210/2211; 631/337/100/101; 631/337/176; CCCTC-Binding Factor - genetics; CCCTC-Binding Factor - metabolism; Cellular structure; Chromatin; Chromatin - genetics; Chromosomes - metabolism; Cohesin; Complexity; Differentiation (biology); Division of labor; Gene expression; Genome; Genomes; Humanities and Social Sciences; Labor; multidisciplinary; Regulatory sequences; Regulatory Sequences, Nucleic Acid; Science; Science (multidisciplinary); Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34276-8

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. It is currently not clear how architectural proteins orchestrate chromatin looping at different scales of genome organisation. Here the authors report Hi-TrAC as a proximity ligation-free method to profile genome-wide chromatin interactions at single nucleosome resolution among regulatory elements.