Histone deacetylase activity is required for embryonic stem cell differentiation

Genesis. 2004 Jan;38(1):32-8. doi: 10.1002/gene.10250.

Abstract

Mammalian development requires commitment of cells to restricted lineages, which requires epigenetic regulation of chromatin structure. Epigenetic modifications were examined during in vitro differentiation of murine embryonic stem (ES) cells. Global histone acetylation, a euchromatin marker, declines dramatically within 1 day of differentiation induction and partially rebounds by day 2. Histone H3-Lys9 methylation, a heterochromatin marker, increases during in vitro differentiation. Conversely, the euchromatin marker H3-Lys4 methylation transiently decreases, then increases to undifferentiated levels by day 4, and decreases by day 6. Global cytosine methylation, another heterochromatin marker, increases slightly during ES cell differentiation. Chromatin structure of the Oct4 and Brachyury gene promoters is modulated in concert with their pattern of expression during ES cell differentiation. Importantly, prevention of global histone deacetylation by treatment with trichostatin A prevents ES cell differentiation. Hence, ES cells undergo functionally important global and gene-specific remodeling of chromatin structure during in vitro differentiation. genesis 38:32-38, 2004.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetyltransferases / metabolism
  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Chromatin Assembly and Disassembly / drug effects
  • Chromatin Assembly and Disassembly / physiology
  • DNA Methylation / drug effects
  • DNA-Binding Proteins / genetics
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Fetal Proteins / genetics
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / genetics
  • Histone Acetyltransferases
  • Histone Deacetylases / metabolism*
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / genetics
  • Histones / metabolism
  • Hydroxamic Acids / pharmacology
  • Mice
  • Octamer Transcription Factor-3
  • Promoter Regions, Genetic / genetics
  • Protein Methyltransferases
  • Stem Cells / cytology
  • Stem Cells / enzymology*
  • T-Box Domain Proteins / genetics
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Fetal Proteins
  • Histones
  • Hydroxamic Acids
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • T-Box Domain Proteins
  • Transcription Factors
  • trichostatin A
  • Histone Methyltransferases
  • Protein Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Acetyltransferases
  • Histone Acetyltransferases
  • Histone Deacetylases
  • Brachyury protein