Bhattacharya Anuradha, Deng Jian Min, Zhang Zhaoping, Behringer Richard, de Crombrugghe Benoit, Maity Sankar N
Department of Molecular Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer Res. 2003 Dec 1;63(23):8167-72.
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.
为了解哺乳动物异源三聚体CCAAT结合因子CBF(也称为NF-Y)的生理功能,我们通过在小鼠Cbf-b/Nf-ya基因中引入loxP位点,构建了一个条件性Cbf-b小鼠突变体。Cre重组酶的可控表达在体内删除该基因,导致CBF复合物失去DNA结合能力,进而导致CBF介导的转录缺失。删除两个Cbf-b等位基因会导致早期胚胎致死,这表明CBF活性对小鼠早期发育至关重要。在小鼠胚胎成纤维细胞的原代培养中,CBF的条件性失活导致细胞增殖受阻并抑制S期或DNA合成,随后诱导细胞凋亡。我们得出结论,CBF转录因子复合物对细胞增殖和活力至关重要。