Silenced Chromatin: Mechanisms of Transcriptional Repression

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This project will use the model organism, baker's yeast, to investigate both the chromosomal structures that 'silence' (shut down) gene expression and the molecular events that accompany the process by which such silenced genes are subsequently activated (turned on). Yeast genes share many features in common with those of complex organisms, including a 'beads-on-a-string' structure and important regulatory mechanisms. Shutting off specific genes at the right time and in the right place (i.e., within the proper tissue) is critical for normal development, health and survival. Understanding the molecular details of how gene expression is silenced (repressed) is therefore of great interest, all the more so given recent evidence suggesting that the way this happens is remarkably similar in yeast, insects and humans. The goals of this project are: (1) to demonstrate that RNA polymerase, the enzyme responsible for copying the DNA into messenger RNA, is present but rendered incapable of working by the specialized chromosomal structures uniquely seen in silenced genes; (2) to characterize the molecular changes that occur when silenced genes become activated in response to an environmental stimulus, and to compare these alterations with those seen in non-silenced genes that are capable of far higher levels of expression; and (3) to identify the proteins that assist RNA polymerase in overcoming the repressive effects of silenced gene structure during activation and compare these to the repertoire of proteins employed for non-silenced genes. The project will also provide training to post-doctoral, graduate, and undergraduate students.