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PMID:11672531

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Citation

Porse, BT, Pedersen TA, , Xu, X, Lindberg, B, Wewer, UM, Friis-Hansen, L and Nerlov, C (2001) E2F repression by C/EBPalpha is required for adipogenesis and granulopoiesis in vivo. Cell 107:247-58

Abstract

The C/EBPalpha transcription factor is required for differentiation of adipocytes and neutrophil granulocytes, and controls cellular proliferation in vivo. To address the molecular mechanisms of C/EBPalpha action, we have identified C/EBPalpha mutants defective in repression of E2F-dependent transcription and found them to be impaired in their ability to suppress cellular proliferation, and to induce adipocyte differentiation in vitro. Using targeted mutagenesis of the mouse germline, we show that E2F repression-deficient C/EBPalpha alleles failed to support adipocyte and granulocyte differentiation in vivo. These results indicate that E2F repression by C/EBPalpha is critical for its ability to induce terminal differentiation, and thus provide genetic evidence that direct cell cycle control by a mammalian lineage-instructive transcription factor couples cellular growth arrest and differentiation.

Links

PubMed

Keywords

3T3 Cells; Adipocytes/cytology; Alleles; Amino Acid Sequence; Animals; Blotting, Northern; Blotting, Western; CCAAT-Enhancer-Binding Protein-alpha/chemistry; CCAAT-Enhancer-Binding Protein-alpha/metabolism; Cell Cycle Proteins; Cell Differentiation; Cell Division; DNA-Binding Proteins; E2F Transcription Factors; Female; Flow Cytometry; Genes, Reporter; Glutathione Transferase/metabolism; Granulocytes/cytology; Humans; Mice; Mice, Knockout; Mice, Transgenic; Molecular Sequence Data; Mutagenesis, Site-Directed; Ovary/metabolism; Protein Binding; Rats; Sequence Homology, Amino Acid; Tissue Distribution; Transcription Factors/chemistry; Transcription, Genetic

Significance

Annotations

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

RAT:CEBPA

involved_in

GO:0045444: fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:CEBPA

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:CEBPA

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CEBPA

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:E2F1

involved_in

GO:0045599: negative regulation of fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:E2F1

involved_in

GO:0006351: transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:E2F1

enables

GO:0043565: sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:CEBPA

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CEBPA

involved_in

GO:0045444: fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CEBPA

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CEBPA

involved_in

GO:0030851: granulocyte differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CEBPA

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CEBPA

enables

GO:0043565: sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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