RRC ID |
4990
|
著者 |
Sun C, Nakatake Y, Akagi T, Ura H, Matsuda T, Nishiyama A, Koide H, Ko MS, Niwa H, Yokota T.
|
タイトル |
Dax1 binds to Oct3/4 and inhibits its transcriptional activity in embryonic stem cells.
|
ジャーナル |
Mol Cell Biol
|
Abstract |
Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. Transcription factor Oct3/4 is an indispensable factor in the self-renewal of ES cells. In this study, we searched for a protein that would interact with Oct3/4 in ES cells and identified an orphan nuclear hormone receptor, Dax1. The association of Dax1 with Oct3/4 was mediated through the POU-specific domain of Oct3/4. Ectopic expression of Dax1 inhibited Oct3/4-mediated activation of an artificial Oct3/4-responsive promoter. Expression of Dax1 in ES cells also reduced the activities of Nanog and Rex1 promoters, while knockdown of Dax1 increased these activities. Pulldown and gel shift assays revealed that the interaction of Dax1 with Oct3/4 abolished the DNA binding activity of Oct3/4. Chromatin immunoprecipitation assay results showed that Dax1 inhibited Oct3/4 binding to the promoter/enhancer regions of Oct3/4 and Nanog. Furthermore, overexpression of Dax1 resulted in ES cell differentiation. Taken together, these data suggest that Dax1, a novel molecule interacting with Oct3/4, functions as a negative regulator of Oct3/4 in ES cells.
|
巻・号 |
29(16)
|
ページ |
4574-83
|
公開日 |
2009-8-1
|
DOI |
10.1128/MCB.01863-08
|
PII |
MCB.01863-08
|
PMID |
19528230
|
PMC |
PMC2725734
|
MeSH |
Animals
Base Sequence
Cell Differentiation / physiology
Cell Line
DAX-1 Orphan Nuclear Receptor
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Embryonic Stem Cells / cytology
Embryonic Stem Cells / physiology*
Gene Expression Regulation, Developmental*
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism
Humans
Mice
Nanog Homeobox Protein
Octamer Transcription Factor-3 / genetics
Octamer Transcription Factor-3 / metabolism*
Receptors, Retinoic Acid / genetics
Receptors, Retinoic Acid / metabolism*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Transcription, Genetic*
|
IF |
3.611
|
引用数 |
53
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
原核生物(大腸菌) |
pDW363 |