Topoisomerase I regulates open chromatin and controls gene expression in vivo.
DNA topoisomerases regulate the topological state of the DNA double helix and are key enzymes in the processes of DNA replication, transcription and genome stability. Using the fission yeast model Schizosaccharomyces pombe, we investigate genome wide how DNA topoisomerases I and II affect chromatin dynamics and gene expression in vivo. We show that topoisomerase I activity is directly required for efficient nucleosome disassembly at gene promoter regions. Lack of topoisomerase activity results in increased nucleosome occupancy, perturbed histone modifications and reduced transcription from these promoters. Strong correlative evidence suggests that topoisomerase I cooperates with the ATP-dependent chromatin remodeller Hrp1 in nucleosome disassembly. Our study links topoisomerase activity to the maintenance of open chromatin and regulating transcription in vivo.
Department of Biosciences and Nutrition, Center for Biosciences, Karolinska Institutet, Novum, Huddinge, Sweden.
Mickaël
M
Durand-Dubief
Jenna
J
Persson
Ulrika
U
Norman
Edgar
E
Hartsuiker
Karl
K
Ekwall
D002843:Chromatin / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D029702:Schizosaccharomyces pombe Proteins; D012319:RNA Polymerase II; C111321:hrp1 protein, S pombe; D004265:DNA Helicases; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II