Principles of bacterial genome organization, a conformational point of view

Abstract

Bacterial chromosomes are large molecules that need to be highly compacted to fit inside the cells. Chromosome compaction must facilitate and maintain key biological processes such as gene expression and DNA transactions (replication, recombination, repair, and segregation). Chromosome and chromatin 3D-organization in bacteria has been a puzzle for decades. Chromosome conformation capture coupled to deep sequencing (Hi-C) in combination with other "omics" approaches has allowed dissection of the structural layers that shape bacterial chromosome organization, from DNA topology to global chromosome architecture. Here we review the latest findings using Hi-C and discuss the main features of bacterial genome folding.

Keywords: 3D organization; bacterial chromatin; bacterial chromosome; condensins; nucleoid‐associated proteins.

FIGURE 1

Hi‐C contact maps in bacteria. (a) Schematic interpretation of a Hi‐C contact map. The Hi‐C contact map is built using the genome of the bacteria of interest segmented into windows of a defined size (bins). The frequency of contacts between bins is then represented using a heat map. In this heat map, bins with a high frequency of contacts are represented in dark purple, while bins with a low frequency of interactions are represented in light blue. In a canonical contact map, the main diagonal reflects the contacts between genomic loci in cis (1, intra‐arm DNA contacts), while the secondary diagonal represents the contacts between genomic loci between the two chromosome arms (2, inter‐arm DNA contacts). (b) Diversity of bacterial 3D genome folding in the tree of life. The bacterial tree of life is represented in gray, and the red line corresponds to the archaea and eukaryota branching (tree adapted from Zhu et al., 2019). Within this tree, Hi‐C maps of wild‐type bacteria with characterized 3D chromosome folding are displayed. The dynamics in 3D folding along the cell cycle is shown for Streptomyces species in early stages of growth (Middle) versus metabolic differentiation (Late). Hi‐C maps shown here were obtained from published works (Barton et al., ; Böhm et al., ; Deng et al., ; Huang et al., ; Lamy‐Besnier et al., ; Le et al., ; Lioy et al., , ; Lioy, Lorenzi, et al., ; Ren, Liao, Karaboja, et al., ; Ren et al., ; Szafran et al., ; Trussart et al., ; Val et al., ; Wang et al., , ; Yin et al., 2020). Except for C. crescentus, B. subtilis, A. tumefaciens, S. coelicolor, and S. venezuelae, for which contact maps were publicly available, all contact maps were built from the available FASTQ files using the OHCA pipeline (Serizay et al., 2024).

FIGURE 2

The layers of 3D chromosome organization in bacteria. Schematic representation of the distinct layers of bacterial chromosome organization. Gray squares show a layer of magnification, from the naked DNA sequence to the bacterial nucleoid. (1) DNA and supercoiling domains; (2) The bacterial chromatin containing Nucleoid Associated Proteins (NAPs), SMC complexes bound to DNA, and Transcriptionally Induced Domains (TIDs). NAPs are shown as red beads, capable of bending, bridging, wrapping, or oligomerizing onto DNA. The SMC complex is represented as a dimeric ring associated with the kleisin and kite subunits (green and subunits in yellow). Transcribing RNA polymerase is shown as a green complex, with transcribed RNA shown in red. TIDs are illustrated in pink, with inter‐TID interactions represented by a light purple cloud. Other DNA binding proteins were omitted for simplicity; (3) Chromosome Interacting Domains (CIDs) are domains of variable size that change according to the growth conditions, usually defined by long and highly expressed genes or TIDs; (4) SMC complexes are loaded onto the chromosome and promote the long‐range DNA contacts in an ATP‐dependent manner in most bacteria by bringing in close proximity distant genomic regions. (5) The integration of these layers with other out‐of‐equilibrium processes, such as DNA transactions, molecular crowding, and interactions with cellular structures, converges in the formation of the bacterial nucleoid.