The B subunit of the CCAAT box binding transcription factor complex (CBF/NF-Y) is essential for early mouse development and cell proliferation.
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.
Bhattacharya
Anuradha
A
Department of Molecular Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Deng
Jian Min
JM
Zhang
Zhaoping
Z
Behringer
Richard
R
de Crombrugghe
Benoit
B
Maity
Sankar N
SN
D000483:Alleles; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D017353:Gene Deletion; D051379:Mice / Q000196:embryology* / Q000235:genetics; D008810:Mice, Inbred C57BL; D016196:S Phase / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic
D023081:CCAAT-Binding Factor