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 language | English |
|---|---|
| Pages (from-to) | 105-116 |
| Number of pages | 12 |
| Journal | Developmental Cell |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2006 |
| Externally published | Yes |
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