Open AccessDax1 Binds to Oct3/4 and Inhibits Its Transcriptional Activity in Embryonic Stem Cells
Author(s) -
Chuanhai Sun,
Yuhki Nakatake,
Tadayuki Akagi,
Hiroki Ura,
Takehisa Matsuda,
Akira Nishiyama,
Hiroshi Koide,
Minoru S.H. Ko,
Hitoshi Niwa,
Takashi Yokota
Publication year - 2009
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.01863-08
Subject(s) - homeobox protein nanog , biology , chromatin immunoprecipitation , gene knockdown , induced pluripotent stem cell , stem cell , embryonic stem cell , rex1 , sox2 , ectopic expression , cellular differentiation , microbiology and biotechnology , promoter , cell culture , gene expression , genetics , gene
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 ofDax1 inhibited Oct3/4-mediated activation of an artificial Oct3/4-responsive promoter. Expression ofDax1 in ES cells also reduced the activities ofNanog andRex1 promoters, while knockdown ofDax1 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 ofOct3/4 andNanog . Furthermore, overexpression ofDax1 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.