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HMGA2 directly mediates chromatin condensation in association with neuronal fate regulation

Author

Listed:
  • Naohiro Kuwayama

    (The University of Tokyo
    University of California)

  • Tomoya Kujirai

    (The University of Tokyo)

  • Yusuke Kishi

    (The University of Tokyo)

  • Rina Hirano

    (The University of Tokyo)

  • Kenta Echigoya

    (The University of Tokyo)

  • Lingyan Fang

    (The University of Tokyo)

  • Sugiko Watanabe

    (Kumamoto University)

  • Mitsuyoshi Nakao

    (Kumamoto University)

  • Yutaka Suzuki

    (The University of Tokyo)

  • Kei-ichiro Ishiguro

    (Kumamoto University)

  • Hitoshi Kurumizaka

    (The University of Tokyo)

  • Yukiko Gotoh

    (The University of Tokyo
    The University of Tokyo)

Abstract

Identification of factors that regulate chromatin condensation is important for understanding of gene regulation. High-mobility group AT-hook (HMGA) proteins 1 and 2 are abundant nonhistone chromatin proteins that play a role in many biological processes including tissue stem-progenitor cell regulation, but the nature of their protein function remains unclear. Here we show that HMGA2 mediates direct condensation of polynucleosomes and forms droplets with nucleosomes. Consistently, most endogenous HMGA2 localized to transposase 5– and DNase I–inaccessible chromatin regions, and its binding was mostly associated with gene repression, in mouse embryonic neocortical cells. The AT-hook 1 domain was necessary for chromatin condensation by HMGA2 in vitro and in cellulo, and an HMGA2 mutant lacking this domain was defective in the ability to maintain neuronal progenitors in vivo. Intrinsically disordered regions of other proteins could substitute for the AT-hook 1 domain in promoting this biological function of HMGA2. Taken together, HMGA2 may regulate neural cell fate by its chromatin condensation activity.

Suggested Citation

  • Naohiro Kuwayama & Tomoya Kujirai & Yusuke Kishi & Rina Hirano & Kenta Echigoya & Lingyan Fang & Sugiko Watanabe & Mitsuyoshi Nakao & Yutaka Suzuki & Kei-ichiro Ishiguro & Hitoshi Kurumizaka & Yukiko , 2023. "HMGA2 directly mediates chromatin condensation in association with neuronal fate regulation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42094-9
    DOI: 10.1038/s41467-023-42094-9
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    1. Ioana Olan & Masami Ando-Kuri & Aled J. Parry & Tetsuya Handa & Stefan Schoenfelder & Peter Fraser & Yasuyuki Ohkawa & Hiroshi Kimura & Masako Narita & Masashi Narita, 2024. "HMGA1 orchestrates chromatin compartmentalization and sequesters genes into 3D networks coordinating senescence heterogeneity," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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