Histone Deacetylase Activity Is Required for Embryonic Stem Cell Differentiation

Jeong Heon Lee, Suzanne R L Hart, David G. Skalnik

Research output: Contribution to journalArticle

213 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)32-38
Number of pages7
JournalGenesis
Volume38
Issue number1
DOIs
StatePublished - Jan 1 2004
Externally publishedYes

Fingerprint

Histone Deacetylases
Embryonic Stem Cells
Cell Differentiation
Histones
Euchromatin
Methylation
Heterochromatin
Epigenomics
Chromatin
trichostatin A
Chromatin Assembly and Disassembly
Cytosine
Acetylation
Genes
In Vitro Techniques

Keywords

  • Brachyury
  • Cytosine methylation
  • Epigenetics
  • Histone code
  • Oct4

ASJC Scopus subject areas

  • Genetics

Cite this

Histone Deacetylase Activity Is Required for Embryonic Stem Cell Differentiation. / Lee, Jeong Heon; Hart, Suzanne R L; Skalnik, David G.

In: Genesis, Vol. 38, No. 1, 01.01.2004, p. 32-38.

Research output: Contribution to journalArticle

Lee, Jeong Heon ; Hart, Suzanne R L ; Skalnik, David G. / Histone Deacetylase Activity Is Required for Embryonic Stem Cell Differentiation. In: Genesis. 2004 ; Vol. 38, No. 1. pp. 32-38.
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