Transcriptional rewiring of the GcrA/CcrM bacterial epigenetic regulatory system in closely related bacteria
| Autor: | Ivan Erill, Patrick D. Curtis, Satish Adhikari |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Transcription Genetic Gene Expression QH426-470 Genome Biochemistry Epigenesis Genetic Transcriptional regulation Cell Cycle and Cell Division Genetics (clinical) Regulation of gene expression Caulobacter Crescentus 0303 health sciences DNA methylation biology 030302 biochemistry & molecular biology Chemical Reactions Genomics Chromatin Nucleic acids Chemistry Experimental Organism Systems Cell Processes Physical Sciences DNA Nucleotidyltransferases Prokaryotic Models Epigenetics DNA modification Chromatin modification Research Article Chromosome biology Cell biology Computational biology Research and Analysis Methods Methylation Caulobacter Promoter Regions 03 medical and health sciences Bacterial Proteins Genetics Gene Regulation Molecular Biology Gene Ecology Evolution Behavior and Systematics 030304 developmental biology Regulons Bacteria Caulobacter crescentus Gene Expression Profiling Organisms Biology and Life Sciences DNA Caulobacteraceae Gene Expression Regulation Bacterial biology.organism_classification Regulon Animal Studies |
| Zdroj: | PLoS Genetics PLoS Genetics, Vol 17, Iss 3, p e1009433 (2021) |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Transcriptional rewiring is the regulation of different target genes by orthologous regulators in different organisms. While this phenomenon has been observed, it has not been extensively studied, particularly in core regulatory systems. Several global cell cycle regulators are conserved in the Alphaproteobacteria, providing an excellent model to study this phenomenon. First characterized in Caulobacter crescentus, GcrA and CcrM compose a DNA methylation-based regulatory system that helps coordinate the complex life cycle of this organism. These regulators are well-conserved across Alphaproteobacteria, but the extent to which their regulatory targets are conserved is not known. In this study, the regulatory targets of GcrA and CcrM were analyzed by SMRT-seq, RNA-seq, and ChIP-seq technologies in the Alphaproteobacterium Brevundimonas subvibrioides, and then compared to those of its close relative C. crescentus that inhabits the same environment. Although the regulators themselves are highly conserved, the genes they regulate are vastly different. GcrA directly regulates 204 genes in C. crescentus, and though B. subvibrioides has orthologs to 147 of those genes, only 48 genes retained GcrA binding in their promoter regions. Additionally, only 12 of those 48 genes demonstrated significant transcriptional change in a gcrA mutant, suggesting extensive transcriptional rewiring between these organisms. Similarly, out of hundreds of genes CcrM regulates in each of these organisms, only 2 genes were found in common. When multiple Alphaproteobacterial genomes were analyzed bioinformatically for potential GcrA regulatory targets, the regulation of genes involved in DNA replication and cell division was well conserved across the Caulobacterales but not outside this order. This work suggests that significant transcriptional rewiring can occur in cell cycle regulatory systems even over short evolutionary distances. Author summary The degree to which genetic or physiological systems evolve over evolutionary distance is often untested. One can assume that the same system in different organisms will change very little if 1) the evolutionary distance between the organisms is small, 2) the systems perform critical functions, and 3) the organisms have been under similar selective pressures (i.e. the organisms inhabited the same ecological niche). The Alphaproteobacteria offer an excellent opportunity to test this assertion as several critical global transcriptional regulators are conserved throughout this clade. In this study, the regulons of two such global regulators, GcrA and CcrM, in two closely related Alphaproteobacteria that inhabit the same ecological niche were compared and it was found that they regulate vastly different genes. In many cases, genes were present in both organisms, but targeted by a regulator in one organism and not in the other. These results suggest that significant transcriptional rewiring can occur even in a core regulatory system over small evolutionary distances and indicate that conservation of genes and genetic regulators may not be a complete indicator of their physiological function in an organism. |
| Databáze: | OpenAIRE |
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