Publication Date
2-10-2024
Journal
Nature Communications
DOI
10.1038/s41467-024-45386-w
PMID
38341433
PMCID
PMC10858947
PubMedCentral® Posted Date
2-10-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Cell Nucleus, Chromatin, Chromosomes, Promoter Regions, Genetic, Humans, RNA-Binding Proteins, Nuclear Matrix-Associated Proteins, Enhancer Elements, Genetic, Genomics, Computational biology and bioinformatics, Developmental biology, Cell biology, Molecular biology
Abstract
Although emerging evidence indicates that alterations in proteins within nuclear compartments elicit changes in chromosomal architecture and differentiation, the underlying mechanisms are not well understood. Here we investigate the direct role of the abundant nuclear complex protein Matrin3 (Matr3) in chromatin architecture and development in the context of myogenesis. Using an acute targeted protein degradation platform (dTAG-Matr3), we reveal the dynamics of development-related chromatin reorganization. High-throughput chromosome conformation capture (Hi-C) experiments revealed substantial chromatin loop rearrangements soon after Matr3 depletion. Notably, YY1 binding was detected, accompanied by the emergence of novel YY1-mediated enhancer-promoter loops, which occurred concurrently with changes in histone modifications and chromatin-level binding patterns. Changes in chromatin occupancy by Matr3 also correlated with these alterations. Overall, our results suggest that Matr3 mediates differentiation through stabilizing chromatin accessibility and chromatin loop-domain interactions, and highlight a conserved and direct role for Matr3 in maintenance of chromosomal architecture.
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