Global H3.3 dynamic deposition defines its bimodal role in cell fate transition
Fang, H.-T El Farran, C.A Xing, Q.R Zhang, L.-F Li, H Lim, B Loh, Y.-H
Fang, H.-T
El Farran, C.A
Xing, Q.R
Zhang, L.-F
Li, H
Lim, B
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Alternative Title
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. © 2018 The Author(s).
Keywords
histone H3, kruppel like factor 4, mitochondrial DNA, mitogen activated protein kinase, Myc protein, octamer transcription factor 4, transcription factor Otx2, transcription factor Sox2, chaperone, collagen, histone, protein binding, transcriptome, cell, collagen, differentiation, gene expression, genetic analysis, protein, animal cell, Article, cell fate, cell proliferation, cell transdifferentiation, collagen metabolism, collagen synthesis, controlled study, embryo, embryonic stem cell, fibroblast, mouse, nerve cell differentiation, nonhuman, nuclear reprogramming, nucleosome, promoter region, protein expression, animal, cell differentiation, cell lineage, chemistry, chromatin immunoprecipitation, cytology, genetics, HEK293 cell line, heterochromatin, human, MAPK signaling, metabolism, nerve cell, pluripotent stem cell, Retroviridae, software, Animals, Cell Differentiation, Cell Lineage, Chromatin Immunoprecipitation, Collagen, Fibroblasts, HEK293 Cells, Heterochromatin, Histone Chaperones, Histones, Humans, MAP Kinase Signaling System, Mice, Neurons, Nucleosomes, Pluripotent Stem Cells, Protein Binding, Retroviridae, Software, Transcriptome
Source Title
Nature Communications
Publisher
Nature Publishing Group
Series/Report No.
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Date
2018
DOI
10.1038/s41467-018-03904-7
Type
Article