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The B Subunit of the CCAAT Box Binding Transcription Factor Complex (CBF/NF-Y) Is Essential for Early Mouse Development and Cell Proliferation

Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, Texas

To understand the physiological function of the mammalian heterotrimeric CCAAT binding factor CBF, also known as NF-Y, we have generated a conditional Cbf-b mouse mutant by introducing loxP sites in the murine Cbf-b/Nf-ya gene. Controlled expression of Cre recombinase deletes the gene in vivo, which leads to a loss of DNA binding by the CBF complex and hence CBF-mediated transcription. Deletion of both Cbf-b alleles causes early embryo lethality, indicating that CBF activity is essential for early mouse development. In primary cultures of mouse embryonic fibroblasts, conditional inactivation of CBF results in a block in cell proliferation and inhibition of S phase or DNA synthesis, which is followed by induction of apoptosis. We conclude that the CBF transcription factor complex is essential for cell proliferation and viability.

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