Stem cell-specific expression of Dax1 is conferred by STAT3 and Oct3/4 in embryonic stem cells.
Embryonic stem (ES) cells are pluripotent cells derived from inner cell mass of blastocysts. An orphan nuclear receptor, Dax1, is specifically expressed in undifferentiated ES cells and plays an important role in their self-renewal. The regulatory mechanism of Dax1 expression in ES cells, however, remains unknown. In this study, we found that STAT3 and Oct3/4, essential transcription factors for ES cell self-renewal, are involved in the regulation of Dax1 expression. Suppression of either STAT3 or Oct3/4 resulted in down-regulation of Dax1. Reporter assay identified putative binding sites for these factors in the promoter/enhancer region of the Dax1 gene. Chromatin immunoprecipitation analysis suggested the in vivo association of STAT3 and Oct3/4 with the putative sites. Furthermore, gel shift assay indicated that these transcription factors directly bind to their putative binding sites. These results suggest that STAT3 and Oct3/4 control the expression of Dax1 to maintain the self-renewal of ES cells.
Sun
Chuanhai
C
Department of Stem Cell Biology, Graduate School of Medical Science, Kanazawa University, Ishikawa 920-8640, Japan.
Nakatake
Yuhki
Y
Ura
Hiroki
H
Akagi
Tadayuki
T
Niwa
Hitoshi
H
Koide
Hiroshi
H
Yokota
Takashi
T
D000818:Animals; D047369:Chromatin Immunoprecipitation; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; C539966:Nr0b1 protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse