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Cleavage of histone H2A during embryonic stem cell differentiation destabilizes nucleosomes to counteract gene activation - PubMed

6 hours ago
  • #stem cell differentiation
  • #nucleosome stability
  • #histone proteolysis
  • Histone H2A is cleaved by Cathepsin L during mouse embryonic stem cell differentiation, primarily at site L23.
  • The cleaved form of H2A (cH2A) reaches about 1% of total H2A after four days of differentiation and is associated with active gene marks.
  • Preventing H2A proteolysis increases acetylated H2A at promoters in differentiated cells, affecting gene activation.
  • Cleavage disrupts recognition of acetylated H2A by readers like PBAF complex members in pluripotent cells.
  • cH2A-containing nucleosomes are less stable or turn over faster than those with full-length H2A, aiding in silencing pluripotency genes.