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PMID:19816951

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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

Significance

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


See also

References

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