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 a 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 noncoding RNA genes. The wild-type 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 noncoding 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.
Steinmetz
Eric J
EJ
Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin 53706.
Warren
Christopher L
CL
Department of Biochemistry, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin 53706.
Kuehner
Jason N
JN
Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin 53706.
Panbehi
Bahman
B
Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin 53706.
Ansari
Aseem Z
AZ
Department of Biochemistry, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin 53706; The Genome Center, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin 53706.
Brow
David A
DA
Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin 53706. Electronic address: dabrow@wisc.edu.
D047369:Chromatin Immunoprecipitation; D015825:Chromosomes, Fungal / Q000235:genetics; D004265:DNA Helicases; D005656:Fungal Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D016681:Genome, Fungal; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020365:RNA Helicases / Q000235:genetics*; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic
D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D012319:RNA Polymerase II; C542347:SEN1 protein, S cerevisiae; D004265:DNA Helicases; D020365:RNA Helicases