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Science 332 (6032): 963-966

Copyright © 2011 by the American Association for the Advancement of Science

Chromatin "Prepattern" and Histone Modifiers in a Fate Choice for Liver and Pancreas

Cheng-Ran Xu,1 Philip A. Cole,2 David J. Meyers,2 Jay Kormish,1,* Sharon Dent,3 Kenneth S. Zaret1,{dagger}

Abstract: Transcriptionally silent genes can be marked by histone modifications and regulatory proteins that indicate the genes’ potential to be activated. Such marks have been identified in pluripotent cells, but it is unknown how such marks occur in descendant, multipotent embryonic cells that have restricted cell fate choices. We isolated mouse embryonic endoderm cells and assessed histone modifications at regulatory elements of silent genes that are activated upon liver or pancreas fate choices. We found that the liver and pancreas elements have distinct chromatin patterns. Furthermore, the histone acetyltransferase P300, recruited via bone morphogenetic protein signaling, and the histone methyltransferase Ezh2 have modulatory roles in the fate choice. These studies reveal a functional "prepattern" of chromatin states within multipotent progenitors and potential targets to modulate cell fate induction.

1 Institute for Regenerative Medicine, Epigenetics Program, Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
2 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
3 Department of Molecular Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Smithville, TX 78957, USA.

* Present address: Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

{dagger} To whom correspondence should be addressed. E-mail: zaret{at}upenn.edu


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