Sex-determining region Y-box 2 and GA-binding proteins regulate the transcription of liver receptor homolog-1 in early embryonic cells.
Pluripotent stem cells maintain their pluripotency and undifferentiated status through a network of transcription factors. Liver receptor homolog-1 (Lrh-1) is one of these, and regulates the expression of other important transcription factors such as Oct-3/4 and Nanog. In early embryo and embryonic stem (ES) cells, Lrh-1 is transcribed using a unique promoter. In this study, we investigated the transcriptional regulation of embryonic Lrh-1 using ES and embryonal carcinoma F9 cells. Reporter assays, electrophoretic mobility shift assays, and chromatin immunoprecipitation assays demonstrated that Sox2 and Gabp proteins bind to the promoter region of embryonic Lrh-1, and are necessary for its activation. The Sox2 site showed strong promoter activity and affinity for protein binding. Upon differentiation into the parietal endoderm by retinoic acid and cAMP, Lrh-1 promoter activity and transcripts were markedly reduced within 24 h. At the same time, Sox2 and Gabp binding to the promoter region of Lrh-1 were decreased, followed by a reduction of their expression. These results indicate that embryonic Lrh-1 expression is regulated by both Sox2 and Gabp. Our study presents new insights into the transcription factor network of pluripotent stem cells.
Department of Biochemistry, University of Fukui, Fukui 910-1193, Japan; Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
Masafumi
M
Kanno
Department of Biochemistry, University of Fukui, Fukui 910-1193, Japan; Translational Research Center, Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan; Department of Biochemistry, Asahikawa Medical University, Hokkaido 078-8510, Japan. Electronic address: yazawa@asahikawa-med.ac.jp.
Takashi
T
Yazawa
Department of Biochemistry, University of Fukui, Fukui 910-1193, Japan; Translational Research Center, Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan.
Shinya
S
Kawabe
Department of Biochemistry, University of Fukui, Fukui 910-1193, Japan; Translational Research Center, Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan.
Yoshitaka
Y
Imamichi
Department of Biochemistry, University of Fukui, Fukui 910-1193, Japan.
Yoko
Y
Usami
Department of Biochemistry, University of Fukui, Fukui 910-1193, Japan.
Yunfeng
Y
Ju
Department of Biochemistry, University of Fukui, Fukui 910-1193, Japan.
Takehiro
T
Matsumura
Department of Biochemistry, University of Fukui, Fukui 910-1193, Japan; Translational Research Center, Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan.
Tetsuya
T
Mizutani
Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Translational Research Center, Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan.
Shigeharu
S
Fujieda
Department of Biochemistry, University of Fukui, Fukui 910-1193, Japan; Translational Research Center, Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan.
Kaoru
K
Miyamoto
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051268:GA-Binding Protein Transcription Factor / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D051268:GA-Binding Protein Transcription Factor; C431936:Nr5a2 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse
Embryonal carcinoma cell; Embryonic stem cell; GA-binding protein; Liver receptor homolog-1; Sex-determining region Y-box 2; Transcriptional regulation