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

Hai-Tong Fang, Chadi A. EL Farran, Qiao Rui Xing, Li-Feng Zhang, Hu Li (), Bing Lim and Yuin-Han Loh ()
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Hai-Tong Fang: A*STAR Institute of Molecular and Cell Biology
Chadi A. EL Farran: A*STAR Institute of Molecular and Cell Biology
Qiao Rui Xing: A*STAR Institute of Molecular and Cell Biology
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

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03904-7

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