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

被引:4
|
作者
Wen, Zi
Zhang, Weihan
Zhong, Quan
Xu, Jinsheng
Hou, Chunhui
Qin, Zhaohui Steve
Li, Li
机构
[1] Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan
[2] 3D Genomics Research Center, Huazhong Agricultural University, Wuhan
[3] Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen
[4] Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA
[5] Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan
来源
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2022年 / 10卷
基金
中国国家自然科学基金;
关键词
A; B compartment; modularity; transcriptional regulation; chromatin architecture; heterochromatin; PHASE-SEPARATION; ARCHITECTURE; PRINCIPLES; GENOME; TRANSCRIPTOME; ORGANIZATION; PROVIDES; DOMAINS;
D O I
10.3389/fcell.2022.845118
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 similar to 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.
引用
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页数:17
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