Synergy of repression and silencing gradients along the chromosome

J Mol Biol. 2009 Apr 10;387(4):826-39. doi: 10.1016/j.jmb.2009.02.025. Epub 2009 Feb 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Fungal / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Fungal
  • Gene Regulatory Networks
  • Gene Silencing
  • Genes, Fungal
  • Models, Genetic
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / genetics
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism
  • Telomere / genetics

Substances

  • CYC8 protein, S cerevisiae
  • DNA-Binding Proteins
  • Repressor Proteins
  • SIR3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae