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

Zi Wen; Weihan Zhang; Quan Zhong; Jinsheng Xu; Chunhui Hou; Zhaohui Steve Qin; Li Li

doi:10.3389/fcell.2022.845118

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

Front Cell Dev Biol. 2022 Apr 19:10:845118. doi: 10.3389/fcell.2022.845118. eCollection 2022.

Authors

Zi Wen^{1

2}, Weihan Zhang¹, Quan Zhong^{1

2}, Jinsheng Xu^{1

2}, Chunhui Hou³, Zhaohui Steve Qin⁴, Li Li^{1

2

5}

Affiliations

¹ Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan, China.
² 3D Genomics Research Center, Huazhong Agricultural University, Wuhan, China.
³ Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
⁴ Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, United States.
⁵ Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, China.

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.

Keywords: A/B compartment; chromatin architecture; heterochromatin; modularity; transcriptional regulation.