Ferrandiz-Avellano, Maria-JoseMartin-Galiano, Antonio JavierSchvartzman, Jorge Bde la Campa, Adela G2020-04-082020-04-082010-06Nucleic Acids Res. 2010 Jun;38(11):3570-81.0305-1048http://hdl.handle.net/20.500.12105/9488The 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.engVoRhttps://creativecommons.org/licenses/by-nc/4.0/CodonDNA Topoisomerases, Type IDNA Topoisomerases, Type IIDNA, BacterialDNA, SuperhelicalEnzyme InhibitorsNovobiocinRNA, MessengerStreptococcus pneumoniaeTopoisomerase II InhibitorsTranscription, GeneticGene Expression Regulation, BacterialGenome, BacterialAttribution-NonCommercial 4.0 International2017657138113570-8110.1093/nar/gkq1061362-4962Nucleic acids researchopen access