Reference - Detail
|Author||Nakatake Y, Fukui N, Iwamatsu Y, Masui S, Takahashi K, Yagi R, Yagi K, Miyazaki J, Matoba R, Ko MS, Niwa H.|
|Title||Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells.|
|Journal||Mol Cell Biol|
Although the POU transcription factor Oct3/4 is pivotal in maintaining self renewal of embryonic stem (ES) cells, little is known of its molecular mechanisms. We previously reported that the N-terminal transactivation domain of Oct3/4 is required for activation of Lefty1 expression (H. Niwa, S. Masui, I. Chambers, A. G. Smith, and J. Miyazaki, Mol. Cell. Biol. 22:1526-1536, 2002). Here we test whether Lefty1 is a direct target of Oct3/4. We identified an ES cell-specific enhancer upstream of the Lefty1 promoter that contains binding sites for Oct3/4 and Sox2. Unlike other known Oct3/4-Sox2-dependent enhancers, however, this enhancer element could not be activated by Oct3/4 and Sox2 in differentiated cells. By functional screening of ES-specific transcription factors, we found that Krüppel-like factor 4 (Klf4) cooperates with Oct3/4 and Sox2 to activate Lefty1 expression, and that Klf4 acts as a mediating factor that specifically binds to the proximal element of the Lefty1 promoter. DNA microarray analysis revealed that a subset of putative Oct3/4 target genes may be regulated in the same manner. Our findings shed light on a novel function of Oct3/4 in ES cells.
|MeSH||Animals Base Sequence Binding Sites Cell Differentiation Conserved Sequence Embryo, Mammalian / cytology Embryo, Mammalian / metabolism Gene Expression / genetics Genes, Reporter / genetics HMGB Proteins / genetics HMGB Proteins / metabolism* Humans Kruppel-Like Transcription Factors / genetics Kruppel-Like Transcription Factors / metabolism* Left-Right Determination Factors Membrane Proteins / genetics* Membrane Proteins / metabolism Mice Organic Cation Transport Proteins / genetics Organic Cation Transport Proteins / metabolism* Promoter Regions, Genetic / genetics* Protein Binding Sex-Determining Region Y Protein / genetics Sex-Determining Region Y Protein / metabolism* Stem Cells / cytology Stem Cells / metabolism* Transforming Growth Factor beta / genetics* Transforming Growth Factor beta / metabolism|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY|
|DNA material||pLefty1p-luc (RDB10004) pLefty1-luc deltaSacI (RDB07097) pBRPyCAG-Klf4-IP (RDB07102) pBR-PyCAG-Sox21318-IP (RDB10779) tk-luc UTF-1 3' (RDB09806) pUtf1p-luc(1) (RDB11028) pUtf1pluc:Utf1enh (RDB11031) pOct4-luc (RDB09895).|