title: The genome of Streptococcus pneumoniae is organized in topology-reacting gene clusters.
abstract: The transcriptional response of Streptococcus pneumoniae was examined after exposure to the GyrB-inhibitor novobiocin. Topoisomer distributions of an internal plasmid confirmed DNA relaxation and recovery of the native level of supercoiling at low novobiocin concentrations. This was due to the up-regulation of DNA gyrase and the down-regulation of topoisomerases I and IV. In addition, >13% of the genome exhibited relaxation-dependent transcription. The majority of the responsive genes (>68%) fell into 15 physical clusters (14.6-85.6 kb) that underwent coordinated regulation, independently of operon organization. These genomic clusters correlated with AT content and codon composition, showing the chromosome to be organized into topology-reacting gene clusters that respond to DNA supercoiling. In particular, down-regulated clusters were flanked by 11-40 kb AT-rich zones that might have a putative structural function. This is the first case where genes responding to changes in the level of supercoiling in a coordinated manner were found organized as functional clusters. Such an organization revealed DNA supercoiling as a general feature that controls gene expression superimposed on other kinds of more specific regulatory mechanisms.
authors.affiliation: Unidad de Genética Bacteriana, Centro Nacional de Microbiología, Instituto de Salud Carlos III and CIBER Enfermedades Respiratorias, 28220 Majadahonda, Madrid, Spain.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Ferrándiz
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Martín-Galiano
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Schvartzman
authors.forename: Adela G
authors.initials: AG
authors.lastname: de la Campa
mesh_terms: D003062:Codon; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004269:DNA, Bacterial / Q000737:chemistry; D004278:DNA, Superhelical / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D009675:Novobiocin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000201:enzymology / Q000235:genetics*; D059005:Topoisomerase II Inhibitors; D014158:Transcription, Genetic
chemical_list: D003062:Codon; D004269:DNA, Bacterial; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D059005:Topoisomerase II Inhibitors; D009675:Novobiocin; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II