Disease relevance of SWI4

• To explore this hypothesis, we expressed Swi4 and Swi6 in insect cells by using the baculovirus system [1].

High impact information on SWI4

• SWI4 of budding yeast codes for a component of a transcription factor (cell cycle box factor, or CCBF) necessary for G1-specific expression of HO [2].
• The requirement of SWI4 for transcription appears to be direct: each gene contains sites similar to the CCBF-binding site; CCBF binds to the upstream region of HCS26 [2].
• We show that SWI4 is essential for haploid cell viability at high temperature and in a/alpha cells at all temperatures: SWI4-deficient cells arrest as large unbudded cells [2].
• The role of SWI4 and SWI6 in the activity of G1 cyclins in yeast [3].
• Eight high copy number plasmids were identified that allow swi4- strains to grow under nonpermissive conditions [2].

Biological context of SWI4

• Both the sensitivity of swi6 mutants to methyl methanesulfonate and hydroxyurea and the transcriptional defect of hrr25 mutants are rescued by overexpression of SWI4, implicating the SBF complex in the Hrr25/Swi6-dependent response to DNA damage [4].
• In Saccharomyces cerevisiae, the heterodimeric transcription factor SBF (for SCB binding factor) is composed of Swi4 and Swi6 and activates gene expression at the G(1)/S-phase transition of the mitotic cell cycle [5].
• Strains deleted for both MBP1 and SWI4 were inviable, demonstrating that transcriptional activation by MBF and SBF has an important role in the transition from G1 to S phase [6].
• Surprisingly, a preferential requirement for SWI6 over SWI4 is observed in our studies of ACGCGT-dependent reporter gene expression in vivo [7].
• The phenotypes of mutations in Paf1 complex components are exacerbated in the swi4 Delta background, suggesting that the complex acts in a pathway parallel to that controlled by Swi4 [8].

Anatomical context of SWI4

• SBF contains the Swi4 and Swi6 proteins and activates the transcription of G(1) cyclin genes, cell wall biosynthesis genes, and the HO gene [9].

Associations of SWI4 with chemical compounds

• We find that swi4, swi6, and hrr25 mutants, but not mbp1 mutants, are sensitive to hydroxyurea and the DNA-damaging agent methyl methane-sulfonate and are defective in the transcriptional induction of a subset of DNA damage-inducible genes [4].
• Reciprocally, we found that clb5 mutant is hypersensitive to SDS, CFW, latrunculin B, or zymolyase, which suggests that, like the PKC pathway and Swi4, Clb5 is related to cell integrity [10].
• The response to glucose is partially suppressed by inactivation of SWI4, but not MBP1, which is consistent with the dependence of MCB core elements upon the SCB-binding transcription factor (SBF) [11].
• Alanine substitutions in both TPLH repeats of SWI6 reduce its activity but do not affect the stability of the protein or its association with SWI4 [12].

Physical interactions of SWI4

• The Swi6 protein interacts with Swi4 to form the SBF complex and with Mbp1 to form the MBF complex [4].
• Swi4 may bind to nonconsensus sequences in the CLN2 promoter (possibly in addition to consensus sites), or it may act indirectly to regulate CLN2 expression [13].
• With the support of chromatin IP chip data, we also predict a possible variant of the Swi4 binding motif and recover a core motif for Arg80 [14].

Regulatory relationships of SWI4

• The growth and budding defects of swi4 mutants are suppressed by overexpression of PKC1 [15].
• A single copy of SWI4 suppressed the cytokinesis defect [16].
• Nuclear proteins Nut1p and Nut2p cooperate to negatively regulate a Swi4p-dependent lacZ reporter gene in Saccharomyces cerevisiae [17].
• Swi6 associates with Swi4 to activate HO and many other late G(1)-specific transcripts in budding yeast [18].
• Multiple SWI6-dependent cis-acting elements control SWI4 transcription through the cell cycle [19].

Other interactions of SWI4

• Periodic expression of SWI4 and CLN3 may be important for cell cycle progression, as we find that these genes are both haploinsufficient and rate limiting for G1 progression [20].
• Inhibition of the Pkc1 pathway exacerbates the growth and bud emergence defects of swi4 mutants [15].
• We find that another dose-dependent suppressor of swi4 mutants, the novel gene HCS77, encodes a putative integral membrane protein [15].
• Role of Swi4 in cell cycle regulation of CLN2 expression [13].
• We performed DNA microarray analysis and identified other genes whose expression was reduced in both SLT2 and SWI4 deletion strains [5].

References