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, Eran Meshorer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

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 languageAmerican English
Article number910
JournalNature Communications
Volume3
DOIs
StatePublished - 2012

Bibliographical note

Funding Information:
We thank Andreas Nagy (Toronto), Rudolf Jaenisch (Cambridge, MA), En Li (Cambridge, MA), Masaki Okano (Kobe), Thomas Jenuwein (Freiburg) and Yoichi Shinkai (Kyoto) for kindly providing cells and reagents; Cecilia Ostlund and Howard Worman (New York) for kindly providing human LMNA plasmids, Adi Alajem (Jerusalem) for help with experiments, and Tom Misteli for critically reviewing the manuscript. E.M. is the Joseph H. and Belle R. Braun senior Lecturer in Life Sciences. This work was supported by the Safra Foundation, the Israel Science Foundation (ISF 215/07 and 943/09 to EM), the European Union (IRG-206872 and ERC-281781 to EM) and NIH Grant CA079057 (to A.S.). S.M. and H.H. are Edmond J. Safra fellows. The research was partly supported by the Center for Cancer Research, intramural program of the NCI, NIH.

Fingerprint

Dive into the research topics of 'Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation'. Together they form a unique fingerprint.

Cite this