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PMID:18396140

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Citation

Birsoy, K, Chen, Z and Friedman, J (2008) Transcriptional regulation of adipogenesis by KLF4. Cell Metab. 7:339-47

Abstract

While adipogenesis is known to be controlled by a complex network of transcription factors, less is known about the transcriptional cascade that initiates this process. We report here the characterization of Krüppel-like factor 4 (KLF4) as an essential early regulator of adipogenesis. Klf4 is expressed in 3T3-L1 cells within 30 min after exposure to a standard adipogenic cocktail of insulin, glucocorticoids, and IBMX. Knockdown of KLF4 inhibits adipogenesis and downregulates C/EBPbeta levels. KLF4 binds directly to the C/EBPbeta (Cebpb) promoter as shown by chromatin immunoprecipitation and gel shift assays and, together with Krox20, cooperatively transactivates a C/EBPbeta reporter. C/EBPbeta knockdown increases levels of KLF4 and Krox20, suggesting that C/EBPbeta normally suppresses Krox20 and KLF4 expression via a tightly controlled negative feedback loop. KLF4 is specifically induced in response to cAMP, which by itself can partially activate adipogenesis. These data suggest that KLF4 functions as an immediate early regulator of adipogenesis to induce C/EBPbeta.

Links

PubMed PMC2430156 Online version:10.1016/j.cmet.2008.02.001

Keywords

1-Methyl-3-isobutylxanthine/pharmacology; 3T3-L1 Cells; Adipogenesis/genetics; Animals; CCAAT-Enhancer-Binding Protein-beta/genetics; CCAAT-Enhancer-Binding Protein-beta/metabolism; Cell Differentiation; Dexamethasone; Early Growth Response Protein 2/metabolism; Feedback, Physiological; Gene Expression Regulation, Developmental; Insulin; Kruppel-Like Transcription Factors/deficiency; Kruppel-Like Transcription Factors/genetics; Kruppel-Like Transcription Factors/metabolism; Mice; Protein Binding; Transcription, Genetic/genetics; Transcriptional Activation/genetics

Significance

Annotations

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

MOUSE:EGR2

involved_in

GO:0045444: fat cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:EGR2

enables

GO:0001102: RNA polymerase II activating transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q60793

F

Seeded From UniProt

complete

MOUSE:EGR2

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KLF4

enables

GO:0001010: RNA polymerase II sequence-specific DNA-binding transcription factor recruiting activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:KLF4

enables

GO:0001085: RNA polymerase II transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P08152

F

Seeded From UniProt

complete

MOUSE:KLF4

involved_in

GO:0006366: transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KLF4

involved_in

GO:0045444: fat cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KLF4

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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