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Global H3.3 dynamic deposition defines its bimodal role in cell fate transition

Author

Listed:
  • Hai-Tong Fang

    (A*STAR Institute of Molecular and Cell Biology)

  • Chadi A. EL Farran

    (A*STAR Institute of Molecular and Cell Biology
    National University of Singapore)

  • Qiao Rui Xing

    (A*STAR Institute of Molecular and Cell Biology
    Nanyang Technological University)

  • Li-Feng Zhang

    (Nanyang Technological University)

  • Hu Li

    (Mayo Clinic)

  • Bing Lim

    (Genome Institute of Singapore)

  • Yuin-Han Loh

    (A*STAR Institute of Molecular and Cell Biology
    National University of Singapore
    National University of Singapore)

Abstract

H3.3 is a histone variant, which is deposited on genebodies and regulatory elements, by Hira, marking active transcription. Moreover, H3.3 is deposited on heterochromatin by Atrx/Daxx complex. The exact role of H3.3 in cell fate transition remains elusive. Here, we investigate the dynamic changes in the deposition of the histone variant H3.3 during cellular reprogramming. H3.3 maintains the identities of the parental cells during reprogramming as its removal at early time-point enhances the efficiency of the process. We find that H3.3 plays a similar role in transdifferentiation to hematopoietic progenitors and neuronal differentiation from embryonic stem cells. Contrastingly, H3.3 deposition on genes associated with the newly reprogrammed lineage is essential as its depletion at the later phase abolishes the process. Mechanistically, H3.3 deposition by Hira, and its K4 and K36 modifications are central to the role of H3.3 in cell fate conversion. Finally, H3.3 safeguards fibroblast lineage by regulating Mapk cascade and collagen synthesis.

Suggested Citation

  • Hai-Tong Fang & Chadi A. EL Farran & Qiao Rui Xing & Li-Feng Zhang & Hu Li & Bing Lim & Yuin-Han Loh, 2018. "Global H3.3 dynamic deposition defines its bimodal role in cell fate transition," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03904-7
    DOI: 10.1038/s41467-018-03904-7
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