Core transcriptional regulatory circuitry in human embryonic stem cells.
Journal: 2005/November - Cell
ISSN: 0092-8674
Abstract:
The transcription factors OCT4, SOX2, and NANOG have essential roles in early development and are required for the propagation of undifferentiated embryonic stem (ES) cells in culture. To gain insights into transcriptional regulation of human ES cells, we have identified OCT4, SOX2, and NANOG target genes using genome-scale location analysis. We found, surprisingly, that OCT4, SOX2, and NANOG co-occupy a substantial portion of their target genes. These target genes frequently encode transcription factors, many of which are developmentally important homeodomain proteins. Our data also indicate that OCT4, SOX2, and NANOG collaborate to form regulatory circuitry consisting of autoregulatory and feedforward loops. These results provide new insights into the transcriptional regulation of stem cells and reveal how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal.
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Cell 122(6): 947-956

Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells

+5 authors
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138
MIT Computer Science and Artificial Intelligence Laboratory (CSAIL), 32 Vassar Street, Cambridge, Massachusetts 02139
Broad Institute of MIT and Harvard, One Kendall Square, Building 300, Cambridge, Massachusetts 02139
Correspondence: ude.tim.iw@gnuoy
These authors contributed equally to this work.

Summary

The transcription factors OCT4, SOX2, and NANOG have essential roles in early development and are required for the propagation of undifferentiated embryonic stem (ES) cells in culture. To gain insights into transcriptional regulation of human ES cells, we have identified OCT4, SOX2, and NANOG target genes using genome-scale location analysis. We found, surprisingly, that OCT4, SOX2, and NANOG co-occupy a substantial portion of their target genes. These target genes frequently encode transcription factors, many of which are developmentally important homeodomain proteins. Our data also indicate that OCT4, SOX2, and NANOG collaborate to form regulatory circuitry consisting of autoregulatory and feedforward loops. These results provide new insights into the transcriptional regulation of stem cells and reveal how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal.

Summary

Footnotes

Supplemental Data: Supplemental Data include seven figures, seven tables, and Supplemental text and can be found with this article online at http://www.cell.com/cgi/content/full/122/6/■■■/DC1/.

Accession Numbers

All microarray data from this study are available at ArrayExpress at the EBI (http://www.ebi.ac.uk/arrayexpress) under the accession designation E-WMIT-5.

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