Disease relevance of SNF2

• Cloning and sequence analysis of a new open reading frame from Bacillus cereus reveals the relationship to a recently identified family of putative eukaryotic transcription activators similar to the yeast SNF2 gene product [1].
• Cloning of an SNF2/SWI2-related protein that binds specifically to the SPH motifs of the SV40 enhancer and to the HIV-1 promoter [2].

High impact information on SNF2

• Here we show that stable promoter occupancy by SWI/SNF and SAGA in the absence of transcription activators requires the bromodomains of the Swi2/Snf2 and Gcn5 subunits, respectively, and nucleosome acetylation [3].
• BRG1 shares extensive sequence similarity to Drosophila brahma, an activator of homeotic gene expression, and the yeast transcriptional activator SNF2/SW12 [4].
• Characterization of the yeast SWI1, SWI2, and SWI3 genes, which encode a global activator of transcription [5].
• In addition, both brm and SNF2 contain a 77 amino acid motif that is found in other Drosophila, yeast, and human regulatory proteins and may be characteristic of a new family of regulatory proteins [6].
• SWI1, SWI2, and SWI5 are required for transcription from sequences physically separate from and independent of the CACGA4 sequences [7].

Biological context of SNF2

• Deletion analysis shows that the helicase-like region of SNF2 is necessary, but not sufficient, for transcriptional activation [8].
• SNF2 mutation has little effect on H3 acetylation, so SAGA and SWI/SNF recruitment seem to be independent events [9].
• Nevertheless, SNF2 in increased gene dosage did not suppress ino80 mutant phenotypes [10].
• All alleles also caused recessive, temperature-sensitive lethality and a recessive defect in galactose utilization, regardless of the SNF2 genotype [11].
• Here we show that many of these TBP mutants were also lethal in strains with disruptions of either GCN5, encoding the histone acetyltransferase in the SAGA complex, or SWI2, encoding the catalytic subunit of the Swi/Snf chromatin remodeling complex [12].

Anatomical context of SNF2

• In addition, a complex containing one of the SNF2/SWI2 homologues and having an in vitro activity similar to the yeast complex has been partially purified from HeLa cells [13].

Associations of SNF2 with chemical compounds

• In order to investigate this regulation, we transformed wild-type yeast with a PEM1 promoter-lacZ fusion and isolated two mutants, named ric1 and ric2 (regulation by myo-inositol and choline), exhibiting decreased PEM1 expression [14].
• The SNF2 gene was predicted to encode a 194 kDa highly charged protein with a glutamine-rich tract [15].
• Roles of SWI1, SWI2, and SWI3 proteins for transcriptional enhancement by steroid receptors [16].
• Both STH1 and SNF2 contain a putative nucleoside triphosphate-binding site and sequences resembling the consensus helicase motifs [17].
• Nuclear localization of this SNF2-like putative helicase is dependent on a nuclear localization sequence located in the NH2-terminal region [18].

Physical interactions of SNF2

• SNF11 interacts with SNF2 in vitro and copurifies with the SNF-SWI complex from yeast cells [19].
• Stimulation of GAL4 binding by the complex was abolished by a mutant SWI2 subunit, and was increased by the presence of a histone-binding protein, nucleoplasmin [20].
• We identified Swh3 as a protein that interacts with the N terminus of Snf2 in the two-hybrid system [21].
• Swi1 is in a complex with Snf2 in C. albicans, and both proteins are localized in the nucleus independent of the growth form [22].

Regulatory relationships of SNF2

• Mutation of the specific negative regulator of phospholipid synthesis encoded by OPI1 suppressed the inositol auxotrophy of swi2 mutants [23].

Other interactions of SNF2

• Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure [24].
• Functional interdependence of the yeast SNF2, SNF5, and SNF6 proteins in transcriptional activation [25].
• These viable TFIIA mutants were lethal in strains lacking Gcn5, Swi2, or Nhp6 [12].
• SNF11, a new component of the yeast SNF-SWI complex that interacts with a conserved region of SNF2 [19].
• The RAD54 gene, which encodes a protein in the SWI2/SNF2 family, plays an important role in recombination and DNA repair in Saccharomyces cerevisiae [26].

Analytical, diagnostic and therapeutic context of SNF2

• The RIC1 gene was isolated by complementation of the Ino- phenotype of ric1 mutant and its identity was confirmed by genetic cross between the original ric1 mutant and a gene disruptant [14].
• A bifunctional SNF2-lacZ fusion protein was shown by immunofluorescence microscopy to be localized to the nucleus, suggesting that the SNF2 protein is located in the nucleus [15].
• Complementation tests indicated that GAM1 is the same gene as SNF2 which is required for derepression of the SUC2 gene encoding invertase [15].
• We report that expression of the yeast RAD54 gene, a member of the SWI2/SNF2 chromatin remodeling gene family, enhances gene targeting in Arabidopsis by one to two orders of magnitude, from 10(-4) to 10(-3) in WT plants to 10(-2) to 10(-1) [27].
• Sequence analysis of one transcript that showed a profound decrease in expression after cytokine withdrawal revealed it to be a member of the SNF2 family of chromatin remodeling ATPases [18].

References