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

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2022 May 6

PMID 35517497

Authors

Zi Wen

Weihan Zhang

Quan Zhong

Jinsheng Xu

Chunhui Hou

Zhaohui Steve Qin

Li Li

Affiliations

Soon will be listed here.

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 , and 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.

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