E2F repression by C/EBP alpha is required for adipogenesis and granulopoiesis in vivo

The C/EBP alpha transcription factor is required for differentiation of adi pocytes and neutrophil granulocytes, and controls cellular proliferation in vivo. To address the molecular mechanisms of C/EBP alpha action, we have i dentified C/EBP alpha mutants defective in repression of E2F-dependent tran scription and found them to be impaired in their ability to suppress cellul ar proliferation, and to induce adipocyte differentiation in vitro. Using t argeted mutagenesis of the mouse germline, we show that E2F repression-defi cient C/EBP alpha alleles failed to support adipocyte and granulocyte diffe rentiation in vivo. These results indicate that E2F repression by C/EBP alp ha is critical for its ability to induce terminal differentiation, and thus provide genetic evidence that direct cell cycle control by a mammalian lin eageinstructive transcription factor couples cellular growth arrest and dif ferentiation.