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

Author

Listed:
  • Tianxin Liu

    (Harvard Medical School)

  • Qian Zhu

    (Harvard Medical School
    Baylor College of Medicine)

  • Yan Kai

    (Harvard Medical School)

  • Trevor Bingham

    (Boston Children’s Hospital)

  • Stacy Wang

    (Baylor College of Medicine)

  • Hye Ji Cha

    (Harvard Medical School
    Dankook University)

  • Stuti Mehta

    (Harvard Medical School)

  • Thorsten M. Schlaeger

    (Boston Children’s Hospital)

  • Guo-Cheng Yuan

    (Dana-Farber Cancer Institute and Harvard Medical School
    Icahn School of Medicine at Mount Sinai)

  • Stuart H. Orkin

    (Harvard Medical School
    Howard Hughes Medical Institute)

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.

Suggested Citation

  • Tianxin Liu & Qian Zhu & Yan Kai & Trevor Bingham & Stacy Wang & Hye Ji Cha & Stuti Mehta & Thorsten M. Schlaeger & Guo-Cheng Yuan & Stuart H. Orkin, 2024. "Matrin3 mediates differentiation through stabilizing chromatin loop-domain interactions and YY1 mediated enhancer-promoter interactions," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45386-w
    DOI: 10.1038/s41467-024-45386-w
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    1. Amy Pandya-Jones & Yolanda Markaki & Jacques Serizay & Tsotne Chitiashvili & Walter R. Mancia Leon & Andrey Damianov & Constantinos Chronis & Bernadett Papp & Chun-Kan Chen & Robin McKee & Xiao-Jun Wa, 2020. "A protein assembly mediates Xist localization and gene silencing," Nature, Nature, vol. 587(7832), pages 145-151, November.
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