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Title: Global H3.3 dynamic deposition defines its bimodal role in cell fate transition
Authors: Fang, Hai-Tong
EL Farran, Chadi A.
Xing, Qiao Rui
Zhang, Li-Feng
Li, Hu
Lim, Bing
Loh, Yuin-Han
Keywords: Dynamic Deposition
Cell Fate Transition
Issue Date: 2018
Source: Fang, H.-T., EL Farran, C. A., Xing, Q. R., Zhang, L.-F., Li, H., Lim, B., et al. (2018). Global H3.3 dynamic deposition defines its bimodal role in cell fate transition. Nature Communications, 9(1) 1537-.
Series/Report no.: Nature Communications
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.
DOI: 10.1038/s41467-018-03904-7
Rights: © 2018 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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