title: Synergy of repression and silencing gradients along the chromosome.
abstract: The expression of a gene is determined by the transcriptional activators and repressors bound to its regulatory regions. It is not clear how these opposing activities are summed to define the degree of silencing of genes within a segment of the eukaryotic chromosome. We show that the general repressor Ssn6 and the silencing protein Sir3 generate inhibitory gradients with similar slopes over a transcribed gene, even though Ssn6 is considered a promoter-specific repressor of single genes, while Sir3 is a regional silencer. When two repression or silencing gradients flank a gene, they have a multiplicative effect on gene expression. A significant amplification of the interacting gradients distinguishes silencing from repression. When a silencing gradient is enhanced, the distance-dependence of the amplification changes and long-range effects are established preferentially. These observations reveal that repression and silencing proteins can attain different tiers in a hierarchy of conserved regulatory modes. The quantitative rules associated with these modes will help to explain the co-expression pattern of adjacent genes in the genome.
authors.affiliation: Institute of Molecular Biology, University of Zurich, Zurich, Switzerland.
authors.forename: Prasuna
authors.initials: P
authors.lastname: Ratna
authors.forename: Simone
authors.initials: S
authors.lastname: Scherrer
authors.forename: Christoph
authors.initials: C
authors.lastname: Fleischli
authors.forename: Attila
authors.initials: A
authors.lastname: Becskei
mesh_terms: D015825:Chromosomes, Fungal / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D020868:Gene Silencing; D005800:Genes, Fungal; D008957:Models, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics
chemical_list: C065455:CYC8 protein, S cerevisiae; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C084122:SIR3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae