Transcription-replication interactions reveal principles of bacterial genome regulation
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Abstract
Organisms determine the transcription rates of thousands of genes through a few modes of regulation that recur across the genome. These modes interact with a changing cellular environment to yield highly dynamic expression patterns. In bacteria, the relationship between a gene’s regulatory architecture and its expression is well understood for individual model gene circuits. However, a broader perspective of these dynamics at the genome-scale is lacking, in part because bacterial transcriptomics have hitherto captured only a static snapshot of expression averaged across millions of cells. As a result, the full diversity of gene expression dynamics and their relation to regulatory architecture remains unknown. Here we present a novel genome-wide classification of regulatory modes based on each gene’s transcriptional response to its own replication, which we term the Transcription-Replication Interaction Profile (TRIP). We found that the response to the universal perturbation of chromosomal replication integrates biological regulatory factors with biophysical molecular events on the chromosome to reveal a gene’s local regulatory context. While the TRIPs of many genes conform to a gene dosage-dependent pattern, others diverge in distinct ways, including altered timing or amplitude of expression, and this is shaped by factors such as intra-operon position, repression state, or presence on mobile genetic elements. Our transcriptome analysis also simultaneously captures global properties, such as the rates of replication and transcription, as well as the nestedness of replication patterns. This work challenges previous notions of the drivers of expression heterogeneity within a population of cells, and unearths a previously unseen world of gene transcription dynamics.
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When we expanded this analysis to chromosome-wide gene-gene correlations, we discovered a striking ‘X-shaped’ pattern of gene expression covariance (Fig. 1D). Beyond the expected diagonal reflecting coordinated gene expression at the level of operons, the anti-diagonal reflected correlations between genes at a similar distance from the origin of replication, between the “arms” of the circular chromosome, as well as a correlation between genes at the origin and terminus
It would be really interesting to compare the patterns you observe here with the X-like genome inversion patterns that we and others have reported (e.g., see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC16139/). These patterns basically show that the distance a gene is from the origin of replication is conserved but the side of the origin it is on is not.
Those …
When we expanded this analysis to chromosome-wide gene-gene correlations, we discovered a striking ‘X-shaped’ pattern of gene expression covariance (Fig. 1D). Beyond the expected diagonal reflecting coordinated gene expression at the level of operons, the anti-diagonal reflected correlations between genes at a similar distance from the origin of replication, between the “arms” of the circular chromosome, as well as a correlation between genes at the origin and terminus
It would be really interesting to compare the patterns you observe here with the X-like genome inversion patterns that we and others have reported (e.g., see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC16139/). These patterns basically show that the distance a gene is from the origin of replication is conserved but the side of the origin it is on is not.
Those inversion patterns have been seen in some but not all comparisons of closely related bacterial and archaeal genomes. So it seems there are some taxa where the distance a gene is from the origin is not conserved over evolutionary time. It would be interesting to know if these taxa show the X-like patternb you report for gene expression.
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