Extensive Chromatin Structure-Function Associations Revealed by Accurate 3D Compartmentalization Characterization

• Type of Material: Article
• Authors: Zi Wen, Huazhong Agricultural University; Weihan Zhang, Huazhong Agricultural University; Quan Zhong, Huazhong Agricultural University; Jinsheng Xu, Huazhong Agricultural University; Chunhui Hou, Southern University of Science and Technology; Zhaohui Qin, Emory University; Li Li, Huazhong Agricultural University
• Language: English
• Date: 2022-04-19
• Publisher: Emory University Libraries
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Wen, Zhang, Zhong, Xu, Hou, Qin and Li.
• Final Published Version (URL): http://dx.doi.org/10.3389/fcell.2022.845118
• Title of Journal or Parent Work: Frontiers in Cell and Developmental Biology
• Volume: 10
• Start Page: 845118
• End Page: 845118
• Keywords: A/B compartment; chromatin architecture; heterochromatin; modularity; transcriptional regulation
• Research Categories: Biology, Biostatistics

Abstract

A/B compartments are observed in Hi-C data and coincide with eu/hetero-chromatin. However, many genomic regions are ambiguous under A/B compartment scheme. We develop MOSAIC (MOdularity and Singular vAlue decomposition-based Identification of Compartments), an accurate compartmental state detection scheme. MOSAIC reveals that those ambiguous regions segregate into two additional compartmental states, which typically correspond to short genomic regions flanked by long canonical A/B compartments with opposite activities. They are denoted as micro-compartments accordingly. In contrast to the canonical A/B compartments, micro-compartments cover ∼30% of the genome and are highly dynamic across cell types. More importantly, distinguishing the micro-compartments underpins accurate characterization of chromatin structure-function relationship. By applying MOSAIC to GM12878 and K562 cells, we identify CD86, ILDR1 and GATA2 which show concordance between gene expression and compartmental states beyond the scheme of A/B compartments. Taken together, MOSAIC uncovers fine-scale and dynamic compartmental states underlying transcriptional regulation and disease.