title: Foxa1 contributes to the repression of Nanog expression by recruiting Grg3 during the differentiation of pluripotent P19 embryonal carcinoma cells.
abstract: Transcription factor Foxa1 plays a critical role during neural differentiation and is induced immediately after retinoic acid (RA)-initiated differentiation of pluripotent P19 embryonal carcinoma cells, correlated with the downregulated expression of pluripotency-related genes such as Nanog. To study whether Foxa1 participates in the repression of pluripotency factors, we expressed Foxa1 ectopically in P19 cells and identified that Nanog was repressed directly by Foxa1. We confirmed that Foxa1 was able to interact with Grg3, which is a transcriptional corepressor that expresses in P19 cells as well as during RA-induced P19 cell differentiation. Knockdown of Foxa1 or Grg3 delayed the downregulation of Nanog expression during RA-induced P19 cell differentiation. Furthermore, we found that Foxa1 recruited Grg3 to the Nanog promoter -2kb upstream region and switched the promoter to an inactive chromatin status represented by typical modifications in histone H3. Together, our results suggested a critical involvement of Foxa1 in the negative regulation of Nanog expression during the differentiation of pluripotent stem cells.
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Hunan, China.
authors.forename: Tuanhui
authors.initials: T
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Hunan, China.
authors.forename: Sijia
authors.initials: S
authors.lastname: He
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Hunan, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Hunan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Hunan, China. Electronic address: yulihnbme@hnu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Hunan, China. Electronic address: yjtan@hnu.edu.cn.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Tan
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054278:Embryonal Carcinoma Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D000071317:Nanog Homeobox Protein; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D056970:Co-Repressor Proteins; C496500:Foxa1 protein, mouse; D051541:Hepatocyte Nuclear Factor 3-alpha; D006657:Histones; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; C104849:Tle3 protein, mouse; D014212:Tretinoin
keywords: Foxa1 transcription factor; Grg3 corepressor; Histone modification; Nanog; P19 embryonal carcinoma cells