Project 3
RNA Polymerase III Regulation:
Another key question is how signaling pathways communicate environmental status to the transcription machinery. We are developing the RNA polymerase III (Pol III) system to study this question. We recently combined genome-wide chromatin immunoprecipitation with whole-genome occupancy analysis to define the entire Pol III transcriptome and to show how the Pol III machinery redistributes during starvation and stress. We are now interested in understanding how the environment (e.g., nutrient availability, stress), cell signaling, and chromatin structure help regulate Pol III transcription. We and others have shown that RSC occupies virtually all genes transcribed by RNA Pol III, such as tRNAs. Recent published work from Timothy Parnell has shown that RSC alters nucleosome density and positioning at Pol III genes. We have characterized the modifications and dynamic associations of the key regulator of Pol III transcription, Maf1, which links environmental conditions to the Pol III system. Our published work has revealed the basic strategy that allows Maf1 to regulate Pol III; starvation and stress lead to Maf1 dephosphorylation, migration to the nucleus, and attachment to (and inhibition of) RNA polymerase III at Pol III genes throughout the genome. Andrew Oler has recently identified the phosphatase that is primarily responsible for Maf1 dephosphorylation, and is investigating how it is regulated. (This work is supported in part by a grant from the National Institutes of Health.)
