Genome-wide distribution of yeast RNA polymerase II and its control by Sen1 helicase

Functional engagement of RNA polymerase II (Pol II) with eukaryotic chromosomes is a fundamental and highly regulated biological process. Here we present the first high-resolution map of Pol II occupancy across the entire yeast genome. We compared a wild-type strain with a strain bearing a substitution in the Sen1 helicase, which is a Pol II termination factor for non-coding RNA genes. The wildtype pattern of Pol II distribution provides unexpected insights into the mechanisms by which genes are repressed or silenced. Remarkably, a single amino acid substitution that compromises Sen1 function causes profound changes in Pol II distribution over both non-coding and protein-coding genes, establishing an important function of Sen1 in the regulation of transcription. Given the strong similarity of the yeast and human Sen1 proteins, our results suggest that progressive neurological disorders caused by substitutions in the human Sen1 homolog, Senataxin, may be due to misregulation of transcription. Keywords: transcription termination, attenuation, silencing, non-coding RNA, Pol II, ChIP-chip 4 identical arrays tiling the S. cerevisiae genome. Two arrays for wild-type, two arrays for Sen1 mutant. Dye swap. In first of each pair, IP is cy3 and input is cy5. In second of each pair, IP is cy5 and input is cy3. Input is defined as genomic DNA sonicated, amplified, and labeled as in IP (skip crosslinking and antibody steps).