In Saccharomyces cerevisiae , transcriptional silencing of the cryptic mating-type loci HMR and HML requires recognition of DNA sequence elements called silencers by the Sir1 protein, one of four specialized proteins necessary for assembly of silent chromatin in yeast. Sir1p is recruited to silencers through protein-protein interactions with Orc1p, the largest subunit of the Origin Recognition Complex (ORC1), which binds directly to DNA elements within the silencer. The ORC Interaction Region (OIR) in the Sir1C- terminus specifically interacts with the N-terminal BAH domain of Orc1. The Sir1-OIR / Orc1-BAH interaction is well understood at the structural level and is necessary for Sir1 to recognize silencers. Although the Orc1-BAH domain is conserved in all eukaryotes, Sir1 is only conserved in the Saccharomyces genus. By comparing the sequences of Sir1 orthologues, we have identified two regions that are conserved and functionally undefined in the N-terminus. We designate these regions N1 and N2, both of which reside outside of the well-characterized Sir1-OIR. Interestingly, N1 shows significant amino acids similarity with a highly conserved functional region of the OIR. Furthermore, mutations in the N1 region abolish Sir1- dependent silencing. Yeast Two Hybrid protein-protein interaction assays suggest that this region may interact with another BAH-Domain containing proteins. Sir3 is another essential component of silent chromatin that may regulate Sir1 activity by binding the Sir1-N terminus. This work suggests that, Sir1 contains an N- terminal domain that is important for silencing and functions to regulate the Orc1BAH / Sir1-OIR interaction.