Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells

Eran Meshorer, Dhananjay Yellajoshula, Eric George, Peter J. Scambler, David T. Brown, Tom Misteli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

840 Scopus citations

Abstract

Differentiation of embryonic stem (ES) cells from a pluripotent to a committed state involves global changes in genome expression patterns. Gene activity is critically determined by chromatin structure and interactions of chromatin binding proteins. Here, we show that major architectural chromatin proteins are hyperdynamic and bind loosely to chromatin in ES cells. Upon differentiation, the hyperdynamic proteins become immobilized on chromatin. Hyperdynamic binding is a property of pluripotent cells, but not of undifferentiated cells that are already lineage committed. ES cells lacking the nucleosome assembly factor HirA exhibit elevated levels of unbound histones, and formation of embryoid bodies is accelerated. In contrast, ES cells, in which the dynamic exchange of H1 is restricted, display differentiation arrest. We suggest that hyperdynamic binding of structural chromatin proteins is a functionally important hallmark of pluripotent ES cells that contributes to the maintenance of plasticity in undifferentiated ES cells and to establishing higher-order chromatin structure.

Original languageAmerican English
Pages (from-to)105-116
Number of pages12
JournalDevelopmental Cell
Volume10
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

Bibliographical note

Funding Information:
We thank R. McKay and D. Hoeppner for reagents, technical assistance, and for critical comments on the manuscript; S. Henikoff, K. Ahmad, and M. Bustin for reagents; and T. Karpova for technical support. Imaging was performed at the National Cancer Institute Imaging Facility. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. P.J.S. is supported by the British Heart Foundation. D.T.B. is supported by grant MCB0235800 from the National Science Foundation. T.M. is a Fellow of the Keith R. Porter Endowment for Cell Biology.

Keywords

  • DNA
  • Stem cell

Fingerprint

Dive into the research topics of 'Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells'. Together they form a unique fingerprint.

Cite this