Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

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}

Program Specificity for Ptf1a in Pancreas versus Neural Tube Development Correlates with Distinct Collaborating Cofactors and Chromatin Accessibility.
D. M. Meredith, M. D. Borromeo, T. G. Deering, B. H. Casey, T. K. Savage, P. R. Mayer, C. Hoang, K.-C. Tung, M. Kumar, C. Shen, et al. (2013)
Mol. Cell. Biol. 33, 3166-3179
   Abstract »    Full Text »    PDF »
Polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent NR2F1 gene.
K. B. Laursen, N. P. Mongan, Y. Zhuang, M. M. Ng, Y. D. Benoit, and L. J. Gudas (2013)
Nucleic Acids Res. 41, 6430-6443
   Abstract »    Full Text »    PDF »
Small-Molecule Inhibitors of Acetyltransferase p300 Identified by High-Throughput Screening Are Potent Anticancer Agents.
H. Yang, C. E. Pinello, J. Luo, D. Li, Y. Wang, L. Y. Zhao, S. C. Jahn, S. A. Saldanha, J. Planck, K. R. Geary, et al. (2013)
Mol. Cancer Ther. 12, 610-620
   Abstract »    Full Text »    PDF »
Cell culture retains contractile phenotype but epigenetically modulates cell-signaling proteins of excitation-contraction coupling in colon smooth muscle cells.
X.-Z. Shi and S. K. Sarna (2013)
Am J Physiol Gastrointest Liver Physiol 304, G337-G345
   Abstract »    Full Text »    PDF »
Ring1b bookmarks genes in pancreatic embryonic progenitors for repression in adult {beta} cells.
J. van Arensbergen, J. Garcia-Hurtado, M. A. Maestro, M. Correa-Tapia, G. A. Rutter, M. Vidal, and J. Ferrer (2013)
Genes & Dev. 27, 52-63
   Abstract »    Full Text »    PDF »
G9a Histone Methyltransferase Activity in Retinal Progenitors Is Essential for Proper Differentiation and Survival of Mouse Retinal Cells.
K. Katoh, R. Yamazaki, A. Onishi, R. Sanuki, and T. Furukawa (2012)
J. Neurosci. 32, 17658-17670
   Abstract »    Full Text »    PDF »
Molecular Mechanisms Involved in the Synergistic Interaction of the EZH2 Inhibitor 3-Deazaneplanocin A with Gemcitabine in Pancreatic Cancer Cells.
A. Avan, F. Crea, E. Paolicchi, N. Funel, E. Galvani, V. E. Marquez, R. J. Honeywell, R. Danesi, G. J. Peters, and E. Giovannetti (2012)
Mol. Cancer Ther. 11, 1735-1746
   Abstract »    Full Text »    PDF »
Nitric oxide modifies chromatin to suppress ICAM-1 expression during colonic inflammation.
Q. Li and S. K. Sarna (2012)
Am J Physiol Gastrointest Liver Physiol 303, G103-G110
   Abstract »    Full Text »    PDF »
Deconstructing Pancreas Developmental Biology.
C. M. Benitez, W. R. Goodyer, and S. K. Kim (2012)
Cold Spring Harb Perspect Biol 4, a012401
   Abstract »    Full Text »    PDF »
Homeoprotein hhex-induced conversion of intestinal to ventral pancreatic precursors results in the formation of giant pancreata in Xenopus embryos.
H. Zhao, D. Han, I. B. Dawid, T. Pieler, and Y. Chen (2012)
PNAS 109, 8594-8599
   Abstract »    Full Text »    PDF »
Enhancers: emerging roles in cell fate specification.
C.-T. Ong and V. G. Corces (2012)
EMBO Rep. 13, 423-430
   Abstract »    Full Text »    PDF »
Drosophila Polycomb complexes restrict neuroblast competence to generate motoneurons.
J. J. Touma, F. F. Weckerle, and M. D. Cleary (2012)
Development 139, 657-666
   Abstract »    Full Text »    PDF »
Genome-wide survey reveals predisposing diabetes type 2-related DNA methylation variations in human peripheral blood.
G. Toperoff, D. Aran, J. D. Kark, M. Rosenberg, T. Dubnikov, B. Nissan, J. Wainstein, Y. Friedlander, E. Levy-Lahad, B. Glaser, et al. (2012)
Hum. Mol. Genet. 21, 371-383
   Abstract »    Full Text »    PDF »
Epigenetic Modifications of Stem Cells: A Paradigm for the Control of Cardiac Progenitor Cells.
Y. Zhou, J. Kim, X. Yuan, and T. Braun (2011)
Circ. Res. 109, 1067-1081
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882