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PMID:16954384

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Citation

Nakatake, Y, Fukui, N, Iwamatsu, Y, Masui, S, Takahashi, K, Yagi, R, Yagi, K, Miyazaki, J, Matoba, R, Ko, MS and Niwa, H (2006) Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Mol. Cell. Biol. 26:7772-82

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.

Links

PubMed PMC1636862 Online version:10.1128/MCB.00468-06

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:KLF4

enables

GO:0000976: transcription regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:KLF4

enables

GO:0044212: transcription regulatory region DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:KLF4

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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