title: Cross-regulation of the Nanog and Cdx2 promoters.
abstract: The first cell fate choice in the mammalian embryo, the segregation of the inner cell mass (ICM) and trophectoderm (TE), is regulated by the mutually antagonistic effects of the transcription factors, Oct4 and Cdx2, while the pluripotency factor, Nanog, is essential to specify the epiblast. We have analyzed the promoters of Nanog and Cdx2, and have found that these two transcription factors are likewise regulated reciprocally. Using an embryonic stem cell line with conditional TE differentiation, we show that Nanog overexpression suppresses the upregulation of TE markers, while Nanog knockdown upregulates the expression of TE markers. We further show that Nanog and Cdx2 bind to and repress each other's promoters. However, whereas Nanog knockout results in detectable Cdx2 expression in the ICM, we observe no overt disruption of blastocyst development, indicating that Nanog plays a subservient role to Oct4 in segregation of the ICM and TE.
authors: Division of Pediatric Hematology/Oncology, Children's Hospital Boston, Dana Farber Cancer Institute, Boston, MA, USA.
authors: Lingyi
authors: L
authors: Chen
authors: Akiko
authors: A
authors: Yabuuchi
authors: Sarah
authors: S
authors: Eminli
authors: Ayumu
authors: A
authors: Takeuchi
authors: Chi-Wei
authors: CW
authors: Lu
authors: Konrad
authors: K
authors: Hochedlinger
authors: George Q
authors: GQ
authors: Daley
mesh_terms: D000818:Animals; D015415:Biomarkers; D001755:Blastocyst / Q000166:cytology / Q000502:physiology*; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation / Q000502:physiology; D046149:Embryo Culture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology
chemical_list: D015415:Biomarkers; D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D014157:Transcription Factors