Journal
EMBO JOURNAL
Volume 21, Issue 17, Pages 4600-4611Publisher
OXFORD UNIV PRESS
DOI: 10.1093/emboj/cdf468
Keywords
chromatin; gene expression; inheritance; mating type; origin recognition complex
Categories
Funding
- NCI NIH HHS [P01 CA013106, CA13106] Funding Source: Medline
- NIGMS NIH HHS [GM 63716, R01 GM045436, R01 GM063716, GM45436] Funding Source: Medline
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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 Angstrom 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, similar to14-20% 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.
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