A gene regulatory network in mouse embryonic stem cells

doi:10.1073/pnas.0701014104

A gene regulatory network in mouse embryonic stem cells

*Department of Statistics, University of California, Los Angeles, 8125 Math Science Building, Los Angeles, CA 90095;
^†Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138; and
^‡Departments of Statistics, Health Research and Policy, and Biological Sciences, Stanford University, 390 Serra Mall, Stanford, CA 94305

Edited by Philip P. Green, University of Washington School of Medicine, Seattle, WA, and approved August 21, 2007 (received for review February 5, 2007)

Abstract

We analyze new and existing expression and transcription factor-binding data to characterize gene regulatory relations in mouse ES cells (ESC). In addition to confirming the key roles of Oct4, Sox2, and Nanog, our analysis identifies several genes, such as Esrrb, Stat3, Tcf7, Sall4, and LRH-1, as statistically significant coregulators. The regulatory interactions among 15 core regulators are used to construct a gene regulatory network in ESC. The network encapsulates extensive cross-regulations among the core regulators, highlights how they may control epigenetic processes, and reveals the surprising roles of nuclear receptors. Our analysis also provides information on the regulation of a large number of putative target genes of the network.

Footnotes

^§To whom correspondence should be addressed. E-mail: whwong{at}stanford.edu
Author contributions: D.A.M. and W.H.W. designed research; Q.Z. and H.C. performed research; Q.Z. and W.H.W. analyzed data; and Q.Z. and W.H.W. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0701014104/DC1.
Abbreviations:

TF,

transcription factor;

ESC,

ES cell;

EB,

embryoid body;

RA,

retinoic acid.