title: Genome urbanization: clusters of topologically co-regulated genes delineate functional compartments in the genome of Saccharomyces cerevisiae.
abstract: The eukaryotic genome evolves under the dual constraint of maintaining coordinated gene transcription and performing effective DNA replication and cell division, the coupling of which brings about inevitable DNA topological tension. DNA supercoiling is resolved and, in some cases, even harnessed by the genome through the function of DNA topoisomerases, as has been shown in the concurrent transcriptional activation and suppression of genes upon transient deactivation of topoisomerase II (topoII). By analyzing a genome-wide transcription run-on experiment upon thermal inactivation of topoII in Saccharomyces cerevisiae we were able to define 116 gene clusters of consistent response (either positive or negative) to topological stress. A comprehensive analysis of these topologically co-regulated gene clusters reveals pronounced preferences regarding their functional, regulatory and structural attributes. Genes that negatively respond to topological stress, are positioned in gene-dense pericentromeric regions, are more conserved and associated to essential functions, while upregulated gene clusters are preferentially located in the gene-sparse nuclear periphery, associated with secondary functions and under complex regulatory control. We propose that genome architecture evolves with a core of essential genes occupying a compact genomic 'old town', whereas more recently acquired, condition-specific genes tend to be located in a more spacious 'suburban' genomic periphery.
authors.affiliation: Computational Genomics Group, Department of Biology, University of Crete, Herakleion 70013, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Tsochatzidou
authors.affiliation: Computational Genomics Group, Department of Biology, University of Crete, Herakleion 70013, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Malliarou
authors.affiliation: Computational Genomics Group, Department of Biology, University of Crete, Herakleion 70013, Greece.
authors.forename: Nikolas
authors.initials: N
authors.lastname: Papanikolaou
authors.affiliation: Molecular Biology Institute of Barcelona (IBMB), Spanish National Research Council (CSIC), Barcelona 08028, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Roca
authors.affiliation: Computational Genomics Group, Department of Biology, University of Crete, Herakleion 70013, Greece.
authors.forename: Christoforos
authors.initials: C
authors.lastname: Nikolaou
mesh_terms: D000595:Amino Acid Sequence; D002451:Cell Compartmentation / Q000235:genetics; D017124:Conserved Sequence; D004261:DNA Replication; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D063990:Gene Ontology; D016681:Genome, Fungal; D058977:Molecular Sequence Annotation; D005810:Multigene Family; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004271:DNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D004250:DNA Topoisomerases, Type II