Fang, H., EL Farran, C.A., Xing, Q.R. et al. Global H3.3 dynamic deposition defines its bimodal role in cell fate transition. Nat Commun 9, 1537 (2018). https://doi.org/10.1038/s41467-018-03904-7
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.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
H.L. is supported by the funding from the National Institutes of Health (R01CA196631), (R01CA208517) and by a grant from Paul F. Glenn Foundation. Y.-H.L. is supported by the (A*Star Investigatorship research award—1437a00116), (JCO Development Programme Grant—1534n00153) and (NRF Investigatorship grant). Y.-H.L. and L.-F.Z. are supported by the Singapore National Research Foundation under its Cooperative Basic Research Grant administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC/CBRG/0092/2015). We are grateful to the Biomedical Research Council, Agency for Science, Technology and Research, Singapore for research funding.