Disease relevance of ABF1

• The protein product of the cloned BAF1 gene produced in Escherichia coli is able to form specific complexes with DNA fragments containing the conserved element TCN7ACG [1].
• The yeast Rad7/Rad16/Abf1 complex generates superhelical torsion in DNA that is required for nucleotide excision repair [2].

High impact information on ABF1

• Using PBMs, we identified the DNA binding-site sequence specificities of the yeast transcription factors Abf1, Rap1 and Mig1 [3].
• In addition to previously identified targets, Abf1, Rap1 and Mig1 bound to 107, 90 and 75 putative new target intergenic regions, respectively, many of which were upstream of previously uncharacterized open reading frames [3].
• We determined that one such transcription factor, Abf1 (refs. 8-10), associates with Yra1 [4].
• In the postreplicative state, genomic footprints closely resemble those produced in vitro by the purified ORC and ABF1 proteins, indicating that the binding of these proteins to replication origins is not sufficient to drive the initiation of DNA replication [5].
• The predicted amino acid sequence contains a novel sequence motif related to the zinc finger, and the ABF1 protein requires zinc and unmodified cysteine residues for sequence-specific DNA binding [6].

Biological context of ABF1

• Silencers lacking either an autonomously replicating sequence consensus element or the RAP1 binding site are strongly derepressed, whereas the wild-type silencer or a silencer containing a deletion of the binding site for another silencer-binding protein, ABF1, are only weakly affected by hybrid expression [7].
• Phosphorylation of ABF1 is therefore a regulated process [8].
• Autonomously replicating sequence binding factor 1 (ABF1) and repressor/activator protein 1 (RAP1) from budding yeast are multifunctional, site-specific DNA-binding proteins, with roles in gene activation and repression, replication, and telomere structure and function [9].
• Autonomously replicating sequence (ARS)-binding factor 1 (ABF1) is a multifunctional protein involved in transcriptional activation and repression, as well as DNA replication, in yeast [10].
• To examine the effect of ABF1 on expression of the ADH1 gene, we constructed an ADH1-lacZ fusion plasmid [10].

Anatomical context of ABF1

• B-Cell coactivator OBF-1 exhibits unusual transcriptional properties and functions in a DNA-bound Oct-1-dependent fashion [11].

Associations of ABF1 with chemical compounds

• From these findings, we propose that the phosphorylation of ABF1 is involved in glucose repression-derepression of COX6 transcription [8].
• Sequences identical to the ABF1-binding site of S. cerevisiae (-121 to -109) or similar to the GCN4-binding site (-113 to -105) were not clearly protected from DMS in vivo [12].
• CS1 specifically participates in transcriptional silencing and/or repression in a context-dependent manner, whereas CS2 is universally required for all three functions of ABF1 [13].
• We have probed contacts of ABF1 with the DNA-binding site using dimethyl sulfate and potassium permanganate and find that the protein makes extensive contacts with both the major and minor grooves [14].
• ABF1 binds to DNA sequences found in ARS elements and in various transcriptional regulatory elements [15].

Physical interactions of ABF1

• Interestingly, an ABF1-binding site can also functionally replace the ILV1 REB1-binding site [16].
• We found that overexpression of Abf1p in a yeast cell increased transcription of the TBP-encoding gene and that this stimulation depended upon the exact sequence of the Abf1p binding site (ABF1) present in the gene [17].
• The ABF1 binding sites also acted in an orientation-independent manner when a synthetic ABF1 binding site was inserted into the yeast CYC1 gene lacking its transcriptional activation region [10].
• Site-directed mutagenesis of Abf1p binding sites in the ACS1 promoter significantly reduced gene expression in the ume6 mutant, grown under repressing conditions [18].
• Both in the natural rpL45 promoter and in the reconstituted promoter, a Rap1 binding site could functionally replace the Abf1 binding site [19].

Regulatory relationships of ABF1

• ABF1 is a phosphoprotein and plays a role in carbon source control of COX6 transcription in Saccharomyces cerevisiae [8].
• The expression of ADH1 was activated synergistically by both ABF1 binding sites [10].
• The ARO3 gene is (i) activated through a sequence element which binds the multifunctional DNA-binding protein ABF1 in vitro and (ii) repressed through an URS1 element, which binds the same protein in vitro as the URS1 element in the CAR1 promoter [20].
• Our results indicate that ABF1 may be involved in the transcriptional control of the yeast tryptophan permease gene [21].
• The SMK1 promoter contains an upstream activating sequence (UASS) that specifically interacts with the transcriptional activator Abf1p [22].

Other interactions of ABF1

• The yeast ARS binding factor 1 (ABF1)--where ARS is an autonomously replicating sequence--and repressor/activator protein 1 (RAP1) have been implicated in DNA replication, transcriptional activation, and transcriptional silencing [6].
• This suggests that ABF1 and REB1 may have related functions within the cell [16].
• We show that the greater the phosphorylation of ABF1, the greater the transcription of COX6 [8].
• It has consensus binding sequences for ABF1 and HAP2 [23].
• A mutated ABF1 site that displays a very low affinity for ABF1 does not functionally replace the ILV1 REB1 site [16].

Analytical, diagnostic and therapeutic context of ABF1

• A gel mobility shift assay showed that ABF1 bound in vitro to both ABF1 binding sites in the promoter and coding regions [10].
• Site-directed mutagenesis of REB1 and ABF1 binding sites demonstrated uncoupling of RNA polymerase I-dependent termination from transcriptional activation in vivo [24].
• Molecular cloning and characterization of the Saccharomyces cerevisiae SAB1 gene that suppresses a temperature-sensitive phenotype of the ARS-binding factor 1 mutant [25].
• Normal and mutant ABF1 proteins were purified by affinity chromatography and their DNA binding activities were analyzed [26].
• A S. cerevisiae ABF1-gene-specific probe showed only weak hybridization with Kluyveromyces DNA and Northern blots did not show a signal [27].

References