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Author(s): Boyer LA; Lee TI; Cole MF; Johnstone SE; Levine SS; Zucker JR; Guenther MG; Kumar RM; Murray HL; Jenner RG; Gifford DK; Melton DA; Jaenisch R; Young RA
Title: Core transcriptional regulatory circuitry in human embryonic stem cells
Source: CELL 122 (6): 947-956
Date: 2005 SEP 23
Document Type: Journal : Article
DOI:
Language: English
Comment:
Address: Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Howard Hughes Med Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. MIT, CSAIL, Cambridge, MA 02139 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. Reprint: Young, RA, Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA
02142 USA. E-mail: young@wi.mit.edu
Author Keywords:
KeyWords Plus: GENE-EXPRESSION; ESCHERICHIA-COLI; NETWORK MOTIFS; HUMAN BLASTOCYSTS;
ES CELLS; MOUSE; DIFFERENTIATION; PLURIPOTENCY; SOX2; ENHANCER
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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