RRC ID 4990
Author Sun C, Nakatake Y, Akagi T, Ura H, Matsuda T, Nishiyama A, Koide H, Ko MS, Niwa H, Yokota T.
Title Dax1 binds to Oct3/4 and inhibits its transcriptional activity in embryonic stem cells.
Journal 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.
Volume 29(16)
Pages 4574-83
Published 2009-8
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 3.813
Times Cited 45
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
Prokaryotes E. coli pDW363