Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing

Nature. 1996 May 16;381(6579):251-3. doi: 10.1038/381251a0.

Abstract

Transcriptional silencing of the HM mating-type loci in the yeast Saccharomyces cerevisiae is caused by the localized formation of an altered chromatin structure, analogous to heterochromatin in higher eukaryotes. Silencing depends on cis-acting sequences, termed silencers, as well as several trans-acting factors, including histones H4 and H3, proteins RAP1 and ABF1, and the four SIR proteins (SIR1-4). Each of the four HM silencers contains an autonomously replicating sequence (ARS) to which the origin replication complex (ORC) binds. This six-protein complex is required for initiation of DNA replication, as well as for silencing. Efficient establishment of the silenced state requires both passage through the S phase of the cell cycle and SIR1 protein. Previous experiments suggested that SIR1 might be localized to the silencers by binding to ORC and/or RAP1. Here we report that SIR1 can bind directly to ORC1, the largest of the ORC subunits, and that targeting of SIR1 to ORC1 at a silencer is sufficient to establish a silenced state.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • DNA, Fungal / metabolism
  • DNA-Binding Proteins / metabolism
  • Fungal Proteins / metabolism
  • Fungal Proteins / physiology*
  • Gene Expression Regulation, Fungal*
  • Histone Deacetylases*
  • Models, Genetic
  • Mutation
  • Protein Binding
  • Recombinant Fusion Proteins / metabolism
  • Replication Origin / physiology*
  • Saccharomyces cerevisiae / genetics*
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae*
  • Sirtuin 2
  • Sirtuins
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*
  • Transcription, Genetic / physiology*

Substances

  • DNA, Fungal
  • DNA-Binding Proteins
  • Fungal Proteins
  • Recombinant Fusion Proteins
  • SIR1 protein, S cerevisiae
  • SIR3 protein, S cerevisiae
  • SIR4 protein, S cerevisiae
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Trans-Activators
  • SIR2 protein, S cerevisiae
  • Sirtuin 2
  • Sirtuins
  • Histone Deacetylases