The genomic DNA of all organisms must be condensed to fit within the confines of cells that are typically several thousand-fold smaller than the DNA itself. Compaction of bacterial chromosomes results in the formation of a structure called the nucleoid. Recent studies in E. coli have revealed a multilayered organization that includes long-range chromosome condensation based on large distinct regions termed macrodomains. There are four MDs (Ori, Right, Left, and Ter), which can be classified as separately organized portions of the nucleoid enclosed within cages of about 0.2 µm in diameter. Each of these domains contains approximately 1 Mbp of DNA. The Ori domain contains oriC. The Ter domain contains the replication termination site. The Left and Right MDs are adjacent to Ter and are separated from the Ori MD by two so-called nonstructured regions. Ongoing studies performed in the host laboratory have revealed that different strategies have been selected for structuring MDs. While the structuring of the Ori MD relies on a unique organizing centre, the organization of Ter, Left and Right MDs involves multiple specific determinants dispersed within the domains. In recent years, we revealed the molecular bases for structuring the Ter MD: the binding of the MatP protein to a 13 bp motif called matS repeated 23 times in the 800 kb long region is required to condense DNA and control the segregation of Ter MD. By performing a structure-function analysis of MatP, we further identified the molecular bases for MatP-mediated Ter condensation and MD formation. MatP contains a newly described tripartite fold that includes a four-helix bundle, a ribbon-helix-helix (RHH) domain and a C-terminal coiled-coil. While the four-helix bundle contains the DNA binding domain and the RHH the determinants for the formation of MatP dimer, the coiled-coils of MatP dimers form a bridged tetramer that flexibly link distant matS sites. Mutating the residues involved in the tetramerization affected DNA condensation within the Ter MD. We thus revealed for the first time a protein-mediated DNA-looping mechanism leading to chromosome condensation in bacteria. Studies showed that chromosome choreography and segregation are tightly controlled during the cell cycle and the MDs have defined positions in the cell throughout the cell cycle. Our results showed that the structuring of the Ter MD is important to ensure faithful chromosome distribution to daughter cells as MatP inactivation leads to severe defects in chromosome segregation. The persistent localization of the Ter MD at mid-cell before cell division relies on the specific interaction of MatP with the protein ZapB associated to the division apparatus. Remarkably, the anchoring of the Ter region to the division apparatus induces a constraining process that can spread in cis to the rest of the chromosome. A site-specific insulation involving 2 insulators flanking the Ter MD has been selected to restrict to the Ter region the consequences of anchoring the Ter MD to the divisome. These results demonstrated a tight coupling between chromosome organization and cell division in E. coli. The present project has three specific aims. Firstly we wish to characterize the in vivo organization of the Ter MD by analyzing the distribution of MatP molecules in the cell, by unveiling the spatial arrangement of the Ter MD DNA, by studying the consequences of altering MatP or matS sites distribution and by identifying the parameters required for the formation of the Ter MD. Secondly, we want to characterize the molecular bases responsible for the structuring of the Ori, Left and Right MDs by identifying the factors and the associated molecular mechanisms. A number of candidates which inactivation affects MD properties have already been identified. Finally, we want to characterize the role of MDs in chromosome management and study how these processes are integrated in the control of the cell cycle.