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Histone crotonylation promotes mesoendodermal commitment of human embryonic stem cells.

Yi Fang1, Xiaojiang Xu2, Jun Ding3

  • 1Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.

Cell Stem Cell
|January 15, 2021
PubMed
Summary

Histone crotonylation, a widespread modification, is vital for endoderm differentiation. Enhancing this process promotes stem cell commitment, while its disruption impairs development, offering therapeutic potential.

Keywords:
crotonylationembryogenesisembryonic stem cellsendoderm differentiationepigeneticsmetabolic switch

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Area of Science:

  • Epigenetics and Developmental Biology
  • Molecular Biology
  • Stem Cell Research

Background:

  • Histone crotonylation is a widespread histone modification, yet its physiological roles are largely unknown.
  • Understanding novel epigenetic modifications is crucial for deciphering cellular differentiation processes.

Purpose of the Study:

  • To investigate the role of histone crotonylation in endoderm differentiation.
  • To identify the molecular mechanisms linking histone crotonylation to endodermal gene expression and cell fate commitment.

Main Methods:

  • Utilized human embryonic stem cells (hESCs) and mouse embryos for in vitro and in vivo studies.
  • Analyzed the induction of crotonyl-coenzyme A (CoA)-producing enzymes during differentiation.
  • Assessed the impact of chemical enhancement and genetic deletion of these enzymes on histone crotonylation levels and differentiation outcomes.

Main Results:

  • Key crotonyl-CoA-producing enzymes are specifically induced during endoderm differentiation.
  • Increased histone crotonylation enhances endodermal gene expression and promotes hESC differentiation.
  • Deletion of crotonyl-CoA-producing enzymes reduces histone crotonylation and impairs meso/endoderm differentiation.

Conclusions:

  • Histone crotonylation is a critical epigenetic regulator of endoderm differentiation.
  • This modification promotes the commitment of pluripotent stem cells to the endodermal lineage.
  • The findings suggest potential therapeutic strategies targeting histone crotonylation for diseases involving differentiation defects.