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

Zhiguo Zhang, Mariko K. Hayashi, Olaf Merkel, Bruce Stillman, Rui Ming Xu

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

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 Å 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, ∼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.

Original languageEnglish (US)
Pages (from-to)4600-4611
Number of pages12
JournalEMBO Journal
Volume21
Issue number17
DOIs
StatePublished - Sep 2 2002

Keywords

  • Chromatin
  • Gene expression
  • Inheritance
  • Mating type
  • Origin recognition complex

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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