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Global H3.3 dynamic deposition defines its bimodal role in cell fate transition
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Journal Article
Global H3.3 dynamic deposition defines its bimodal role in cell fate transition
2018
Overview
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.
Histone variant H3.3 is incorporated at transcriptionally active genes and is associated with active marks. Here, the authors investigate H3.3 deposition during reprogramming and find that initially H3.3 helps maintain parental cell fate and is later required for establishment of the cell lineages.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/100
/ 13/89
/ 14
/ 38
/ 38/39
/ 45
/ 45/15
/ 49
/ 49/91
/ Animals
/ Chromatin Immunoprecipitation
/ Collagen
/ Embryos
/ Histone Chaperones - metabolism
/ Humanities and Social Sciences
/ Humans
/ Mice
/ Pluripotent Stem Cells - cytology
/ Science
/ Software
