Mapping Topoisomerase IV Binding and Activity Sites on the E. coli Genome

Hafez El Sayyed (1, 2) , Ludovic Le Chat (1) , Elise Lebailly (3) , Elise Vickridge (2) , Carine Pages (3) , Francois Cornet (3) , Marco Cosentino Lagomarsino (4) , Olivier Espéli (1)

1 CIRB - Centre interdisciplinaire de recherche en biologie
2 Université Paris-Saclay
3 LMGM - Laboratoire de microbiologie et génétique moléculaires - UMR5100
4 LCQB - Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology

Catenation links between sister chromatids are formed progressively during DNA replica-tion and are involved in the establishment of sister chromatid cohesion. Topo IV is a bacterial type II topoisomerase involved in the removal of catenation links both behind replication forks and after replication during the final separation of sister chromosomes. We have investigated the global DNA-binding and catalytic activity of Topo IV in E. coli using genomic and molecular biology approaches. ChIP-seq revealed that Topo IV interaction with the E. coli chromosome is controlled by DNA replication. During replication, Topo IV has access to most of the genome but only selects a few hundred specific sites for its activity. Local chro-matin and gene expression context influence site selection. Moreover strong DNA-binding and catalytic activities are found at the chromosome dimer resolution site, dif, located opposite the origin of replication. We reveal a physical and functional interaction between Topo IV and the XerCD recombinases acting at the dif site. This interaction is modulated by MatP, a protein involved in the organization of the Ter macrodomain. These results show that Topo IV, XerCD/dif and MatP are part of a network dedicated to the final step of chromosome management during the cell cycle.

Domaines: Bio-Informatique, Biologie Systémique [q-bio.QM]; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Hafez El Sayyed, Ludovic Le Chat, Elise Lebailly, Elise Vickridge, Carine Pages, et al.. Mapping Topoisomerase IV Binding and Activity Sites on the E. coli Genome. PLoS Genetics, 2016, 12 (5), pp.e1006025. ⟨10.1371/journal.pgen.1006025⟩. ⟨hal-01527413⟩