Cross-regulation of the Nanog and Cdx2 promoters  

作　　者：Lingyi Chen Akiko Yabuuchi Sarah Eminli Ayumu Takeuchi Chi-Wei Lu Konrad Hochedlinger George Q Daley 

机构地区：[1]Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, MA, USA [2]Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School Boston, MA, USA [3]Division of Hematology, Brigham and Women's Hospital Boston, MA, USA [4]Harvard Stem Cell Institute, Boston, MA, USA [5]Howard Hughes Medical Institute, Boston, MA, USA [6]Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, Boston, MA, USA

出　　处：《Cell Research》2009年第9期1052-1061,共10页细胞研究（英文版）

摘　　要：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.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.

关 键 词：CDX2 NANOG embryonic stem cells trophectoderm stem cells 

分 类 号：Q811.4[生物学—生物工程] Q813