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Dual mitotic bookmarking by GAF and H3K27ac orchestrates differential propagation of cell fate memory in neural development

Author

Listed:
  • Rulan Zhang

    (Peking University)

  • Jie Liu

    (Peking University)

  • Zimo Zhang

    (Peking University
    1650 Owens St)

  • Zili Chen

    (Peking University)

  • Tanpeng Wang

    (Peking University)

  • Yuying Shen

    (Peking University)

  • Zejun Lan

    (Peking University)

  • Jingyi Chu

    (Peking University)

  • Haoxuan Tang

    (Peking University
    Harvard University)

  • Xiyue Zhang

    (Peking University)

  • Yan Song

    (Peking University
    Peking University)

Abstract

In brain development, neural stem cells (NSCs) undergo asymmetric cell divisions to replicate themselves and meanwhile produce differentiating siblings. It remains obscure how NSCs preserve their self-renewing fate across mitosis. Even less is known how cell fate memory is differentially propagated to sibling daughter cells adopting distinct cell fates. Here we found that key differentiation genes are dually bookmarked by pioneer factor GAF (GAGA factor) and H3K27ac in asymmetrically-dividing Drosophila central brain NSCs. In daughter cells adopting NSC fate, GAF promotes self-renewal through timely inhibiting differentiation genes via HDAC1-mediated H3K27 deacetylation, whereas in sibling daughter cells adopting neural progenitor fate, GAF occupancy is replaced by competitor SWI/SNF complex, allowing retention of H3K27ac mark and fast activation of differentiation genes. Thus, our study unveils a paradigm by which cell fate memory can be differentially transmitted to sibling daughter cells via dual antagonistic mitotic bookmarking and selective molecular competition mechanism.

Suggested Citation

  • Rulan Zhang & Jie Liu & Zimo Zhang & Zili Chen & Tanpeng Wang & Yuying Shen & Zejun Lan & Jingyi Chu & Haoxuan Tang & Xiyue Zhang & Yan Song, 2025. "Dual mitotic bookmarking by GAF and H3K27ac orchestrates differential propagation of cell fate memory in neural development," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62974-6
    DOI: 10.1038/s41467-025-62974-6
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    1. Maëlle Bellec & Jérémy Dufourt & George Hunt & Hélène Lenden-Hasse & Antonio Trullo & Amal Zine El Aabidine & Marie Lamarque & Marissa M. Gaskill & Heloïse Faure-Gautron & Mattias Mannervik & Melissa , 2022. "The control of transcriptional memory by stable mitotic bookmarking," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. David V. Hansen & Jan H. Lui & Philip R. L. Parker & Arnold R. Kriegstein, 2010. "Neurogenic radial glia in the outer subventricular zone of human neocortex," Nature, Nature, vol. 464(7288), pages 554-561, March.
    3. Fides Zenk & Yinxiu Zhan & Pavel Kos & Eva Löser & Nazerke Atinbayeva & Melanie Schächtle & Guido Tiana & Luca Giorgetti & Nicola Iovino, 2021. "HP1 drives de novo 3D genome reorganization in early Drosophila embryos," Nature, Nature, vol. 593(7858), pages 289-293, May.
    4. Zhexin Zhu & Xiaolong Chen & Ao Guo & Trishabelle Manzano & Patrick J. Walsh & Kendall M. Wills & Rebecca Halliburton & Sandi Radko-Juettner & Raymond D. Carter & Janet F. Partridge & Douglas R. Green, 2023. "Mitotic bookmarking by SWI/SNF subunits," Nature, Nature, vol. 618(7963), pages 180-187, June.
    5. Mahé Raccaud & Elias T. Friman & Andrea B. Alber & Harsha Agarwal & Cédric Deluz & Timo Kuhn & J. Christof M. Gebhardt & David M. Suter, 2019. "Mitotic chromosome binding predicts transcription factor properties in interphase," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    6. Emil F. Michelotti & Suzanne Sanford & David Levens, 1997. "Marking of active genes on mitotic chromosomes," Nature, Nature, vol. 388(6645), pages 895-899, August.
    7. Elizabeth D. Larson & Hideyuki Komori & Tyler J. Gibson & Cyrina M. Ostgaard & Danielle C. Hamm & Jack M. Schnell & Cheng-Yu Lee & Melissa M. Harrison, 2021. "Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
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