Structure and function of the BAH-containing domain of Orc1p in epigenetic silencing

EMBO J. 2002 Sep 2;21(17):4600-11. doi: 10.1093/emboj/cdf468.


The N-terminal domain of the largest subunit of the Saccharomyces cerevisiae origin recognition complex (Orc1p) functions in transcriptional silencing and contains a bromo-adjacent homology (BAH) domain found in some chromatin-associated proteins including Sir3p. The 2.2 A crystal structure of the N-terminal domain of Orc1p revealed a BAH core and a non-conserved helical sub-domain. Mutational analyses demonstrated that the helical sub-domain was necessary and sufficient to bind Sir1p, and critical for targeting Sir1p primarily to the cis-acting E silencers at the HMR and HML silent chromatin domains. In the absence of the BAH domain, approximately 14-20% of cells in a population were silenced at the HML locus. Moreover, the distributions of the Sir2p, Sir3p and Sir4p proteins, while normal, were at levels lower than found in wild-type cells. Thus, in the absence of the Orc1p BAH domain, HML resembled silencing of genes adjacent to telomeres. These data are consistent with the view that the Orc1p-Sir1p interaction at the E silencers ensures stable inheritance of pre-established Sir2p, Sir3p and Sir4p complexes at the silent mating type loci.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Chromatin / metabolism
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / physiology
  • Gene Expression Regulation, Fungal*
  • Gene Silencing*
  • Histone Deacetylases / metabolism
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Origin Recognition Complex
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae*
  • Sirtuin 2
  • Sirtuins
  • Structure-Activity Relationship
  • Trans-Activators / metabolism
  • Transcription, Genetic


  • Chromatin
  • DNA-Binding Proteins
  • Macromolecular Substances
  • Origin Recognition Complex
  • SIR1 protein, S cerevisiae
  • SIR3 protein, S cerevisiae
  • SIR4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Trans-Activators
  • SIR2 protein, S cerevisiae
  • Sirtuin 2
  • Sirtuins
  • Histone Deacetylases

Associated data

  • PDB/1M4Z