Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation

Shai Melcer, Hadas Hezroni, Eyal Rand, Malka Nissim-Rafinia, Arthur I. Skoultchi, Colin L. Stewart, Michael Bustin, Eran Meshorer

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Embryonic stem cells are characterized by unique epigenetic features including decondensed chromatin and hyperdynamic association of chromatin proteins with chromatin. Here we investigate the potential mechanisms that regulate chromatin plasticity in embryonic stem cells. Using epigenetic drugs and mutant embryonic stem cells lacking various chromatin proteins, we find that histone acetylation, G9a-mediated histone H3 lysine 9 (H3K9) methylation and lamin A expression, all affect chromatin protein dynamics. Histone acetylation controls, almost exclusively, euchromatin protein dynamics; lamin A expression regulates heterochromatin protein dynamics, and G9a regulates both euchromatin and heterochromatin protein dynamics. In contrast, we find that DNA methylation and nucleosome repeat length have little or no effect on chromatin-binding protein dynamics in embryonic stem cells. Altered chromatin dynamics associates with perturbed embryonic stem cell differentiation. Together, these data provide mechanistic insights into the epigenetic pathways that are responsible for chromatin plasticity in embryonic stem cells, and indicate that the genome's epigenetic state modulates chromatin plasticity and differentiation potential of embryonic stem cells.

Original languageEnglish (US)
Article number910
JournalNature Communications
Volume3
DOIs
StatePublished - 2012

Fingerprint

Histone Code
Lamin Type A
chromatin
stem cells
Embryonic Stem Cells
Stem cells
Histones
Chromatin
Cell Differentiation
proteins
Proteins
Epigenomics
plastic properties
Euchromatin
acetylation
Plasticity
Acetylation
methylation
Heterochromatin
Methylation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation. / Melcer, Shai; Hezroni, Hadas; Rand, Eyal; Nissim-Rafinia, Malka; Skoultchi, Arthur I.; Stewart, Colin L.; Bustin, Michael; Meshorer, Eran.

In: Nature Communications, Vol. 3, 910, 2012.

Research output: Contribution to journalArticle

Melcer, Shai ; Hezroni, Hadas ; Rand, Eyal ; Nissim-Rafinia, Malka ; Skoultchi, Arthur I. ; Stewart, Colin L. ; Bustin, Michael ; Meshorer, Eran. / Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation. In: Nature Communications. 2012 ; Vol. 3.
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AU - Rand, Eyal

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AU - Skoultchi, Arthur I.

AU - Stewart, Colin L.

AU - Bustin, Michael

AU - Meshorer, Eran

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