Inner nuclear protein Matrin-3 coordinates cell differentiation by stabilizing chromatin architecture
Year: 2021
Type: article
Abstract: Precise control of gene expression during differentiation relies on the interplay of chromatin and nuclear structure. Despite an established contribution of nuclear membrane proteins to developmental gene regulation, little is known regarding the role of inner nuclear proteins. Here we demonstrate that loss of the nuclear scaffolding protein Matrin-3 (Matr3) in erythroid cells leads to morphological and gene expression changes characteristic of accelerated maturation, as well as broad alterations in chromatin organization similar to those accompanying differentiation. Matr3 protein interacts with CTCF and the cohesin complex, and its loss perturbs their occupancy at a subset of sites. Destabilization of CTCF and cohesin binding correlates with altered transcription and accelerated differentiation. This association is conserved in embryonic stem cells. Our findings indicate Matr3 negatively affects cell fate transitions and demonstrate that a critical inner nuclear protein impacts occupancy of architectural factors, culminating in broad effects on chromatin organization and cell differentiation.
Source: Nature Communications
Institutions: Boston Children's Hospital, Harvard University, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, University of Massachusetts Chan Medical School, Broad Institute, Brigham and Women's Hospital, Children's Medical Center, The University of Texas Southwestern Medical Center, Howard Hughes Medical Institute
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: Howard Hughes Medical Institute, U.S. Department of Health and Human Services, Harvard T.H. Chan School of Public Health, National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Investigating the Mechanisms of Cohesinopathy in Myelodysplastic Syndromes, G2694610121, Big Omics Data Engine 2 Supercomputer, DEVELOPMENTAL BIOLOGY OF HUMAN ERYTHROPOIESIS, G4539474206, A systems biology approach for dissecting enhancer hierarchy, G7077071163, Systems Biology Analysis of Human Erythropoiesis, Targeting Metabolic Liabilities of Leukemia-Initiating Cells (R01CA230631), Molecular Analysis of Transcriptional Enhancers in Hematopoiesis
OpenAlex ID: W3208292419