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 journalArticle

80 Citations (Scopus)

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
Pages (from-to)4600-4611
Number of pages12
JournalEMBO Journal
Volume21
Issue number17
DOIs
Publication statusPublished - 2002 Sep 2
Externally publishedYes

Fingerprint

Epigenomics
Chromatin
Origin Recognition Complex
Telomere
Gene Silencing
Yeast
Saccharomyces cerevisiae
Proteins
Genes
Crystal structure
Population

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Zhang, Z., Hayashi, M. K., Merkel, O., Stillman, B., & Xu, R. M. (2002). Structure and function of the BAH-containing domain of Orc1p in epigenetic silencing. EMBO Journal, 21(17), 4600-4611. https://doi.org/10.1093/emboj/cdf468

Structure and function of the BAH-containing domain of Orc1p in epigenetic silencing. / Zhang, Zhiguo; Hayashi, Mariko K.; Merkel, Olaf; Stillman, Bruce; Xu, Rui Ming.

In: EMBO Journal, Vol. 21, No. 17, 02.09.2002, p. 4600-4611.

Research output: Contribution to journalArticle

Zhang, Z, Hayashi, MK, Merkel, O, Stillman, B & Xu, RM 2002, 'Structure and function of the BAH-containing domain of Orc1p in epigenetic silencing', EMBO Journal, vol. 21, no. 17, pp. 4600-4611. https://doi.org/10.1093/emboj/cdf468
Zhang, Zhiguo ; Hayashi, Mariko K. ; Merkel, Olaf ; Stillman, Bruce ; Xu, Rui Ming. / Structure and function of the BAH-containing domain of Orc1p in epigenetic silencing. In: EMBO Journal. 2002 ; Vol. 21, No. 17. pp. 4600-4611.
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