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Publication : Histone crotonylation promotes mesoendodermal commitment of human embryonic stem cells.

First Author  Fang Y Year  2021
Journal  Cell Stem Cell Volume  28
Issue  4 Pages  748-763.e7
PubMed ID  33450185 Mgi Jnum  J:306264
Mgi Id  MGI:6710394 Doi  10.1016/j.stem.2020.12.009
Citation  Fang Y, et al. (2021) Histone crotonylation promotes mesoendodermal commitment of human embryonic stem cells. Cell Stem Cell 28(4):748-763.e7
abstractText  Histone crotonylation is a non-acetyl histone lysine modification that is as widespread as acetylation. However, physiological functions associated with histone crotonylation remain almost completely unknown. Here we report that histone crotonylation is crucial for endoderm differentiation. We demonstrate that key crotonyl-coenzyme A (CoA)-producing enzymes are specifically induced in endodermal cells during differentiation of human embryonic stem cells (hESCs) in vitro and in mouse embryos, where they function to increase histone crotonylation and enhance endodermal gene expression. Chemical enhancement of histone crotonylation promotes endoderm differentiation of hESCs, whereas deletion of crotonyl-CoA-producing enzymes reduces histone crotonylation and impairs meso/endoderm differentiation in vitro and in vivo. Our study uncovers a histone crotonylation-mediated mechanism that promotes endodermal commitment of pluripotent stem cells, which may have important implications for therapeutic strategies against a number of human diseases.
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