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 Skoultchi, Colin L. Stewart, Michael Bustin and Eran Meshorer ()
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Shai Melcer: The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra campus 91904, Israel.
Hadas Hezroni: The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra campus 91904, Israel.
Eyal Rand: Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bldg. 37, Bethesda, Maryland 20892, USA.
Malka Nissim-Rafinia: The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra campus 91904, Israel.
Arthur Skoultchi: Albert Einstein College of Medicine
Colin L. Stewart: Institute of Medical Biology, 8A Biomedical Drive Singapore
Michael Bustin: Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bldg. 37, Bethesda, Maryland 20892, USA.
Eran Meshorer: The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra campus 91904, Israel.

Nature Communications, 2012, vol. 3, issue 1, 1-12

Abstract: 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.

Date: 2012
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DOI: 10.1038/ncomms1915

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