In Saccharomyces cerevisiae, Silent information regulator (Sir) proteins are required for regional gene silencing at the silent mating type cassettes and telomeres. The initiation of transcriptional silencing at these domains is proposed to involve the recruitment of the Sir complex, composed of Sir2, Sir3, and Sir4, by DNA-binding proteins. This recruitment is followed by iterative cycles of NAD dependent deacetylation, production of O-acetyl-ADP-ribose, and binding of Sir3 and Sir4 to the deacetylated nucleosomes, and leads to the creation of extended silent chromatin domains. These silenced regions have histones that are hypoacetylated and hypomethylated,while disruption of enzymes that acetylate and methylatehistones leads to mislocalization of Sir3. Thus, histonemodifications play a crucial role in the assembly of silent chromatin.However, while Sir3 has been shown to have histone and nucleosome binding properties in vitro, specific binding of Sir3 tonucleosomes, as it occurs in vivo, has yet to be observed. We show that the Bromo-adjacent-homology (BAH) domain of Sir3 is necessary for nucleosome binding and that this binding is regulated byhistone acetylation and methylation. These results suggest that theBAH domain, found in many eukaryotic chromatin proteins, binds to specifically modified nucleosomes.
