Disease relevance of CBF1

• Disruption of the CBF1 gene caused a decrease in the growth rate, an increase in the rate of chromosome loss/nondisjunction, and hypersensitivity to the antimitotic drug thiabendazole [1].
• When expressed in Escherichia coli, the CP1 gene directed the synthesis of a CDEI-binding protein having the same gel mobility as purified yeast CP1 [2].
• CP1-binding sites occurred not only at centromeres but also near many transcription units, for example, adjacent to binding sites for the GAL4-positive regulatory protein upstream of the GAL2 gene in S. cerevisiae and adjacent to the TATA element of the adenovirus major late promoter [3].

Psychiatry related information on CBF1

• We have cloned and determined the nucleotide sequence of the gene (CBF2) specifying the large (110 kD) subunit of the 240-kD multisubunit yeast centromere binding factor CBF3, which binds selectively in vitro to yeast centromere DNA and contains a minus end-directed microtubule motor activity [4].

High impact information on CBF1

• Cohesin association with a centromere depends on Mif2p, the centromere binding factor CBF3, and a centromere-specific histone variant, Cse4p [5].
• Unexpectedly, the cbf1 null mutation concomitantly resulted in a methionine auxotrophic phenotype, which suggests that CBF1, like other HLH proteins in higher eukaryotic cells, participates in the regulation of gene expression [1].
• DNA sequence analysis of the CBF1 gene reveals homology with the transforming protein myc and a family of regulatory proteins known as the helix-loop-helix (HLH) proteins [1].
• Ndc10p and Cbf1p, previously implicated in centromere function by genetic and in vitro biochemical assays, were also found to interact with centromeric DNA in vivo [6].
• Situated upstream of the sulfur genes, this element is the binding site of a transcription activation complex consisting of a basic helix-loop-helix factor, Cbf1p, and two basic leucine zipper factors, Met4p and Met28p [7].

Chemical compound and disease context of CBF1

• Deletion of the gene encoding Cbf1p results in an increased frequency of chromosome loss, hypersensitivity to low levels of microtubule disrupting drugs (such as thiabendazole and benomyl) and methionine auxotrophy [8].

Biological context of CBF1

• Mutations in genes encoding CBF1 and CBF3, proteins that bind to yeast centromeres, interfere with chromosome segregation in vivo [9].
• MET4, a leucine zipper protein, and centromere-binding factor 1 are both required for transcriptional activation of sulfur metabolism in Saccharomyces cerevisiae [10].
• The modulation of MET gene expression by GCN4 can explain discrepancies in the literature regarding CP1 dependence of MET gene transcription [11].
• Taken together, these data suggest that the Mif2 protein interacts with Cep1p at the centromere and that the yeast centromere indeed exists as a higher order protein-DNA complex [12].
• In addition, the mif2 temperature-sensitive phenotype can be partially rescued by increased dosage of CEP1 [12].

Anatomical context of CBF1

• CBP1 associates with the Dictyostelium cytoskeleton and is important for normal cell aggregation under certain developmental conditions [13].
• In vivo analysis of sequences necessary for CBP1-dependent accumulation of cytochrome b transcripts in yeast mitochondria [14].

Associations of CBF1 with chemical compounds

• However, we show that induction of the sulfate assimilation pathway is not achieved solely by CBF1 [10].
• The enhanced transcription was dependent on the CBF1 gene, but did not compete with an excess of wild-type Met4p, suggesting that some changes in the affinity of Met4p to other factors might be involved in S-adenosylmethionine-mediated transcriptional regulation [15].
• Role of the Saccharomyces cerevisiae general regulatory factor CP1 in methionine biosynthetic gene transcription [11].
• C. glabrata cells containing the CBF1 gene under the influence of a shutdown promoter (tetO-ScHOP) arrested their growth after 5 h of cultivation in the presence of the reactive drug doxycycline [16].
• We find that CBF3 is absolutely essential for this attachment but, contrary to previous reports (Hyman, A. A., K. Middleton, M. Centola, T.J. Mitchison, and J. Carbon. 1992. Microtubule-motor activity of a yeast centromere-binding protein complex. Nature (Lond.). 359:533-536) is not sufficient [9].

Physical interactions of CBF1

• Cbf1p is a sequence specific DNA binding protein required for MET16 chromatin remodelling and transcription [17].
• In addition, the CBF1 transcriptional activator can interact with the ARABIDOPSIS GCN5 and ADA2 proteins [18].
• Moreover, Met28 is shown to enhance the DNA-binding activity of Cbf1 [19].
• The multifunctional DNA-binding proteins ABF1 and CPF1 bind in a mutually exclusive manner to the promoter region of the QCR8 gene, which encodes 11-kDa subunit VIII of the Saccharomyces cerevisiae mitochondrial ubiquinol-cytochrome c oxidoreductase (QCR) [20].
• Cbf1p has been shown to interact with the chromatin-remodeling ATPase Isw1p [21].

Regulatory relationships of CBF1

• Functional analyses after the separate introduction of point mutations into both elements reveal no role for the latter protein and only a minor role for Cpf1p in the regulated expression of CYT1/lacZ chimaeric proteins [22].
• Physical and functional interactions of Arabidopsis ADA2 transcriptional coactivator proteins with the acetyltransferase GCN5 and with the cold-induced transcription factor CBF1 [23].
• Detailed analyses of the LAC1 promoter demonstrated that transcription of this gene is inhibited by the presence of the transcription factor Cbf1p and the anaerobic repressor Rox1p [24].

Other interactions of CBF1

• MET16-CYC1-lacZ reporter constructs were used to show that MET16 5'-flanking DNA contains a CP1-dependent upstream activation sequence (UAS) [11].
• Synthetic lethal interactions between a cep1 null mutation and mutations in either NDC10 or CEP3 were also detected [12].
• The requirement for Met4 in regulating GSH1 expression is lost in the absence of the centromere-binding protein Cbf1 [25].
• The suppressing plasmids contained either CEP1 or DNA derived from the PHO4 locus [26].
• Spontaneously arising extragenic suppressors of cep1 methionine auxotrophy were also isolated; approximately one-third of them were alleles of pho80 [26].

Analytical, diagnostic and therapeutic context of CBF1

• Here we tested whether all potential Cbf1p binding motifs in the yeast genome are likely to be bound by Cbf1p using chromatin immunoprecipitation [21].
• We have determined the apparent equilibrium dissociation constants of Cbf1p binding to all 16 CDEI DNAs in gel retardation assays [27].
• In mammalian and yeast two-hybrid assays, these mutations were also associated with a loss of CBF1-mediated transcriptional repression and a severely impaired interaction with the corepressors SMRT and CIR [28].
• To examine the activity of CBP1, we generated temperature-sensitive cbp1 mutant strains by polymerase chain reaction (PCR) mutagenesis and in vivo recombination [29].
• In cbp1 mutant strains, cytochrome b gene (cob) transcripts are not detectable by Northern blot analysis [30].

References