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, Yuin Han Loh

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Article number1537
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Histones
Heterochromatin
Embryonic Stem Cells
cells
Collagen
Fibroblasts
stem cells
fibroblasts
Transcription
collagens
Stem cells
genes
marking
cascades
depletion
Genes
synthesis
Cellular Reprogramming

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Fang, H. T., El Farran, C. A., Xing, Q. R., Zhang, L. F., Li, H., Lim, B., & Loh, Y. H. (2018). Global H3.3 dynamic deposition defines its bimodal role in cell fate transition. Nature Communications, 9(1), [1537]. https://doi.org/10.1038/s41467-018-03904-7

Global H3.3 dynamic deposition defines its bimodal role in cell fate transition. / Fang, Hai Tong; El Farran, Chadi A.; Xing, Qiao Rui; Zhang, Li Feng; Li, Hu; Lim, Bing; Loh, Yuin Han.

In: Nature Communications, Vol. 9, No. 1, 1537, 01.12.2018.

Research output: Contribution to journalArticle

Fang, Hai Tong ; El Farran, Chadi A. ; Xing, Qiao Rui ; Zhang, Li Feng ; Li, Hu ; Lim, Bing ; Loh, Yuin Han. / Global H3.3 dynamic deposition defines its bimodal role in cell fate transition. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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