PMID:19816951

Citation	Wei, Z, Yang, Y, Zhang, P, Andrianakos, R, Hasegawa, K, Lyu, J, Chen, X, Bai, G, Liu, C, Pera, M and Lu, W (2009) Klf4 interacts directly with Oct4 and Sox2 to promote reprogramming. Stem Cells 27:2969-78
Abstract	Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by ectopic expression of specific sets of transcription factors. Oct4, Sox2, and Klf4, factors that share many target genes in embryonic stem (ES) cells, are critical components in various reprogramming protocols. Nevertheless, it remains unclear whether these factors function together or separately in reprogramming. Here we show that Klf4 interacts directly with Oct4 and Sox2 when expressed at levels sufficient to induce iPS cells. Endogenous Klf4 also interacts with Oct4 and Sox2 in iPS cells and in mouse ES cells. The Klf4 C terminus, which contains three tandem zinc fingers, is critical for this interaction and is required for activation of the target gene Nanog. In addition, Klf4 and Oct4 co-occupy the Nanog promoter. A dominant negative mutant of Klf4 can compete with wild-type Klf4 to form defective Oct4/Sox2/Klf4 complexes and strongly inhibit reprogramming. In the absence of Klf4 overexpression, interaction of endogenous Klf4 with Oct4/Sox2 is also required for reprogramming. This study supports the idea that direct interactions between Klf4, Oct4, and Sox2 are critical for somatic cell reprogramming.
Links	PubMed Online version:10.1002/stem.231
Keywords	Animals; Cells, Cultured; Humans; Induced Pluripotent Stem Cells/metabolism; Kruppel-Like Transcription Factors/genetics; Kruppel-Like Transcription Factors/metabolism; Mice; Mutation; Nuclear Reprogramming; Octamer Transcription Factor-3/genetics; Octamer Transcription Factor-3/metabolism; Protein Binding; SOXB1 Transcription Factors/genetics; SOXB1 Transcription Factors/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:PO5F1	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q60793	F		Seeded From UniProt	complete
MOUSE:SOX2	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q60793	F		Seeded From UniProt	complete
MOUSE:KLF4	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P20263	F		Seeded From UniProt	complete
MOUSE:KLF4	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P48432	F		Seeded From UniProt	complete
MOUSE:PO5F1	enables	GO:0008134: transcription factor binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q60793	F		Seeded From UniProt	complete
MOUSE:KLF4	enables	GO:0008134: transcription factor binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P20263	F		Seeded From UniProt	complete
MOUSE:KLF4	enables	GO:0008134: transcription factor binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P48432	F		Seeded From UniProt	complete
MOUSE:KLF4	involved_in	GO:0019827: stem cell population maintenance	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:KLF4	involved_in	GO:0045595: regulation of cell differentiation	ECO:0000314: direct assay evidence used in manual assertion		P		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
MOUSE:SOX2	enables	GO:0008134: transcription factor binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q60793	F		Seeded From UniProt	complete

References

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