Nucleosome binding relinquishes the association of the BAH domain of Orc1 with Sir1

Mating-type switching in S. cerevisiae requires silencing of the homothallic mating (HM) loci through formation of position-dependent, gene-independent repressive chromatin domains, resembling heterochromatic regions in higher eukaryotes. Genetic and biochemical studies have identified cis -acting DNA elements, called silencers, and trans -acting protein factors important for the establishment and maintenance of the silent chromatin. Yet, the molecular mechanism governing the position-dependence of gene silencing is not fully understood. Here we report that the BAH domain of Orc1, which is responsible for recruiting Sir1 to the Orc1-bound silencers, ceases to bind Sir1 in the presence of nucleosome. This finding suggests a unified role of sensing the chromatin environment by Orc1’s BAH domain in transcriptional silencing and specification of replication origins. We further dissected the structural determinants of the BAH domain required for binding Sir1. These results expanded the understanding of Orc1’s functions in epigenetic silencing of the HM loci.