title: Topoisomerase II binds nucleosome-free DNA and acts redundantly with topoisomerase I to enhance recruitment of RNA Pol II in budding yeast.
abstract: DNA topoisomerases are believed to promote transcription by removing excessive DNA supercoils produced during elongation. However, it is unclear how topoisomerases in eukaryotes are recruited and function in the transcription pathway in the context of nucleosomes. To address this problem we present high-resolution genome-wide maps of one of the major eukaryotic topoisomerases, Topoisomerase II (Top2) and nucleosomes in the budding yeast, Saccharomyces cerevisiae. Our data indicate that at promoters Top2 binds primarily to DNA that is nucleosome-free. However, although nucleosome loss enables Top2 occupancy, the opposite is not the case and the loss of Top2 has little effect on nucleosome density. We also find that Top2 is involved in transcription. Not only is Top2 enriched at highly transcribed genes, but Top2 is required redundantly with Top1 for optimal recruitment of RNA polymerase II at their promoters. These findings and the examination of candidate-activated genes suggest that nucleosome loss induced by nucleosome remodeling factors during gene activation enables Top2 binding, which in turn acts redundantly with Top1 to enhance recruitment of RNA polymerase II.
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, and the Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Sperling
authors.forename: Kyeong Soo
authors.initials: KS
authors.lastname: Jeong
authors.forename: Tasuku
authors.initials: T
authors.lastname: Kitada
authors.forename: Michael
authors.initials: M
authors.lastname: Grunstein
mesh_terms: D047369:Chromatin Immunoprecipitation; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism*; D016681:Genome, Fungal / Q000235:genetics; D009154:Mutation; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D028081:Proton-Phosphate Symporters / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004271:DNA, Fungal; D009707:Nucleosomes; C105495:PHO84 protein, S cerevisiae; D028081:Proton-Phosphate Symporters; D029701:Saccharomyces cerevisiae Proteins; D012319:RNA Polymerase II; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II