Cross-regulation of the Nanog and Cdx2 promoters.
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.
Chen
Lingyi
L
Division of Pediatric Hematology/Oncology, Children's Hospital Boston, Dana Farber Cancer Institute, Boston, MA, USA.
Yabuuchi
Akiko
A
Eminli
Sarah
S
Takeuchi
Ayumu
A
Lu
Chi-Wei
CW
Hochedlinger
Konrad
K
Daley
George Q
GQ
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
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