title: Core transcriptional regulatory circuitry in human embryonic stem cells.
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.
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Boyer
authors.forename: Tong Ihn
authors.initials: TI
authors.lastname: Lee
authors.forename: Megan F
authors.initials: MF
authors.lastname: Cole
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Johnstone
authors.forename: Stuart S
authors.initials: SS
authors.lastname: Levine
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Zucker
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Guenther
authors.forename: Roshan M
authors.initials: RM
authors.lastname: Kumar
authors.forename: Heather L
authors.initials: HL
authors.lastname: Murray
authors.forename: Richard G
authors.initials: RG
authors.lastname: Jenner
authors.forename: David K
authors.initials: DK
authors.lastname: Gifford
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Melton
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
authors.forename: Richard A
authors.initials: RA
authors.lastname: Young
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D017690:Cell Transplantation / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005809:Genes, Regulator / Q000235:genetics / Q000502:physiology*; D024002:HMGB Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D055748:SOXB1 Transcription Factors; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors