PT - JOURNAL ARTICLE AU - Maria Tsochatzidou AU - Maria Malliarou AU - Nikolas Papanikolaou AU - Joaquim Roca AU - Christoforos Nikolaou TI - Genome urbanization: Clusters of topologically co-regulated genes delineate functional compartments in the genome of <em>S. cerevisiae</em> AID - 10.1101/064667 DP - 2017 Jan 01 TA - bioRxiv PG - 064667 4099 - http://biorxiv.org/content/early/2017/01/24/064667.short 4100 - http://biorxiv.org/content/early/2017/01/24/064667.full AB - The eukaryotic genome evolves under the dual constraint of maintaining co-ordinated 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 run-on experiment upon thermal inactivation of topoII in S.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 revealed 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 up-regulated gene clusters are preferentially located in the gene-sparse nuclear periphery, associated with secondary functions and under complex regulatory control. We propose that 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.