The studies described here have focused on elucidating how Sir-mediated silent chromatin regulates gene transcription and what determinants may affect the linear diffusion of Sir complex along chromatin template in the yeast Saccharomyces cerevisiae. The studies pinpoint the transition between polymerase initiation and elongation as the step targeted by Sir2, and indicate that transcriptional silencing is achieved through the differential accessibility of initiation and capping/elongation factors to chromatin. The mechanisms by which SIR modulates gene activation are also...