Control of bacterial chromosome replication by non-coding regions outside the origin

Abstract

Chromosome replication in Eubacteria is initiated by initiator protein(s) binding to specific sites within the replication origin, oriC. Recently, initiator protein binding to chromosomal regions outside the origin has attracted renewed attention; as such binding sites contribute to control the frequency of initiations. These outside-oriC binding sites function in several different ways: by steric hindrances of replication fork assembly, by titration of initiator proteins away from the origin, by performing a chaperone-like activity for inactivation- or activation of initiator proteins or by mediating crosstalk between chromosomes. Here, we discuss initiator binding to outside-oriC sites in a broad range of different taxonomic groups, to highlight the significance of such regions for regulation of bacterial chromosome replication. For Escherichia coli, it was recently shown that the genomic positions of regulatory elements are important for bacterial fitness, which, as we discuss, could be true for several other organisms.

Evolution of Complex Regulation for Cell-Cycle Control

“…In E. coli , where gene copy number distribution is dominated by the growth cycle, transcriptomic data has revealed that the position of many genes correlates with their time of expression during the growth cycle ( Sobetzko et al, 2012 ). Yet even certain binding sites for DnaA in E. coli have been shown to play a position-dependent role in cell-cycle regulation ( Frimodt-Møller et al, 2017 ).…”

“…Prokaryotes also have complex biochemistry available to exploit the physical genome organization. Cooperative binding of transcription factors to DNA ( Hermsen et al, 2006 ) or regulation beyond the level of transcription ( Bryant et al, 2014 ; Frimodt-Møller et al, 2017 ; Krogh et al, 2018 ) would only seem to provide more routes for evolution to couple replication to regulation. In C. crescentus , chromatin states are used to control gene expression during the cell cycle ( Collier et al, 2007 ; Seong et al, 2021 ).…”

Evolution of Regulatory Complexity for Cell-Cycle Control

“…It is remarkable that functional genome organization evolved via these mentioned mechanisms even when many complex physical features were not included in the model. Cooperative binding of transcription factors to DNA (Hermsen et al, 2006) or regulation beyond the level of transcription (Bryant et al, 2014;Frimodt-Møller et al, 2017;Krogh et al, 2018) would only seem to provide more routes for evolution to couple replication to regulation. In C. crescentus, chromatin states are used to control gene expression during the cell-cycle (Collier et al, 2007;Seong et al, 2021).…”

“…In Escherichia coli, where the growth cycle dominates replication, transcriptomic data has revealed that the position of many genes correlates with their time of expression during the growth cycle (Sobetzko et al, 2012). Yet even certain binding sites for DnaA in E. coli have been shown to play a position-dependent role in cell-cycle regulation (Frimodt-Møller et al, 2017).…”

Determination of the Optimal Chromosomal Location(s) for a DNA Element in <em>Escherichia coli</em> Using a Novel Transposon-mediated Approach

“…In bacteria, this mainly results from interference by the transcription of neighboring genes, local DNA topology, and/or replication-associated gene dosage. In particular, the processes of DNA replication and segregation are controlled, at least in part, by non-coding chromosomal regions 1 , and the proper function of these regions depends on genomic location/context. In E.coli, examples are the dif site, required for sister chromosome resolution 2 ; KOPS sequences, required for chromosome segregation 3 ; and datA, DARS1, and DARS2 regions, required for proper chromosomal replication control (below; 4 ).…”