The B subunit of the CCAAT box binding transcription factor complex (CBF/NF-Y) is essential for early mouse development and cell proliferation

Abstract

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.