title: Nanog positively regulates Zfp57 expression in mouse embryonic stem cells.
abstract: To maintain the self-renewal of embryonic stem (ES) cells, several core transcription factors, including Oct3/4, STAT3, and Nanog, regulate the expression of their target genes. Zinc finger protein 57 (Zfp57) is specifically expressed in self-renewing ES cells and its expression level is reduced upon ES cell differentiation, suggesting that expression of this transcription factor is regulated by core transcription factors. In the present study, we investigated whether Zfp57 expression is regulated by Nanog. Nanog overexpression resulted in the upregulation of Zfp57. On the other hand, knockdown of Nanog reduced the expression level of Zfp57. In addition, we identified the Nanog-responsive region in the promoter of the Zfp57 gene. These results suggest that Nanog is an upstream regulator of Zfp57. Moreover, Nanog overexpression promoted the growth of ES cells in soft agar and this was suppressed by Zfp57 knockdown, suggesting that the Nanog/Zfp57 pathway plays a central role in anchorage-independent growth of ES cells. Interestingly, NANOG overexpression also led to the upregulation of ZFP57 in two human tumor cell lines. Taken together, our results suggest that Nanog positively regulates Zfp57 expression in multiple types of cells.
authors.affiliation: Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan. Electronic address: takamuh@staff.kanazawa-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamura
authors.affiliation: Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Akagi
authors.affiliation: Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Oyama
authors.affiliation: Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Tajima
authors.affiliation: Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kitagawa
authors.affiliation: Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Fushida
authors.affiliation: Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokota
authors.affiliation: Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan. Electronic address: hkoide@med.kanazawa-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koide
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D019073:HT29 Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D000071317:Nanog Homeobox Protein; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C531063:ZFP57 protein, human
keywords: Anchorage-independent growth; Cancer; ES cells; Nanog; Zfp57