Matrin3 mediates differentiation through stabilizing chromatin loop-domain interactions and YY1 mediated enhancer-promoter interactions.

Autor: Liu T; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, 02115, USA., Zhu Q; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, 02115, USA.; Lester Sue Smith Breast Center, Department of Human Molecular Genetics, Baylor College of Medicine, 1 Moursund St, Houston, TX, 77030, USA., Kai Y; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, 02115, USA., Bingham T; Stem Cell Program, Boston Children's Hospital, Boston, MA, 02115, USA., Wang S; Lester Sue Smith Breast Center, Department of Human Molecular Genetics, Baylor College of Medicine, 1 Moursund St, Houston, TX, 77030, USA., Cha HJ; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, 02115, USA.; Department of Biomedical Science & Engineering, Dankook University, Cheonan, 31116, South Korea., Mehta S; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, 02115, USA., Schlaeger TM; Stem Cell Program, Boston Children's Hospital, Boston, MA, 02115, USA., Yuan GC; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, 02115, USA.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Orkin SH; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, 02115, USA. stuart_orkin@dfci.harvard.edu.; Howard Hughes Medical Institute, Boston, MA, 02115, USA. stuart_orkin@dfci.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 10; Vol. 15 (1), pp. 1274. Date of Electronic Publication: 2024 Feb 10.
DOI: 10.1038/s41467-024-45386-w
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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