RRC ID 28453
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
Abstract 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.
Volume 26(20)
Pages 7772-82
Published 2006-10-1
DOI 10.1128/MCB.00468-06
PII MCB.00468-06
PMID 16954384
PMC PMC1636862
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
IF 3.735
Times Cited 190
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
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).