Transcriptional rewiring of the GcrA/CcrM bacterial epigenetic regulatory system in closely related bacteria

dc.contributor.authorAdhikari, Satish
dc.contributor.authorErill, Ivan
dc.contributor.authorCurtisI, Patrick D.
dc.date.accessioned2021-03-26T16:52:50Z
dc.date.available2021-03-26T16:52:50Z
dc.date.issued2021-03-11
dc.description.abstractTranscriptional 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.en_US
dc.description.sponsorshipWe are grateful to Doug Rusch and Ram Podicheti at the Center for Genomics and Bioinformatics at Indiana University, Bloomington for their support in RNA-sequencing and data analysis. We would also like to thank David Kudrna and Dario Copetti at Arizona Genomics Institute, University of Arizona for their support in SMRT sequencing. Similarly, we are also thankful to Jason Steel and Shanshan Yang for their support in ChIP-sequencing and data analysis. Lastly, we thank members of the Curtis lab for their support.en_US
dc.description.urihttps://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009433en_US
dc.format.extent30 pagesen_US
dc.genrejournal articlesen_US
dc.identifierdoi:10.13016/m2moeb-5izc
dc.identifier.citationAdhikari S, Erill I, Curtis PD (2021) Transcriptional rewiring of the GcrA/CcrM bacterial epigenetic regulatory system in closely related bacteria. PLoS Genet 17(3): e1009433. https://doi.org/10.1371/journal.pgen.1009433en_US
dc.identifier.urihttps://doi.org/10.1371/journal.pgen.1009433
dc.identifier.urihttp://hdl.handle.net/11603/21226
dc.language.isoen_USen_US
dc.publisherPLOSen_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Biological Sciences Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.relation.ispartofUMBC Computer Science and Electrical Engineering Department
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
dc.rightsAttribution 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.titleTranscriptional rewiring of the GcrA/CcrM bacterial epigenetic regulatory system in closely related bacteriaen_US
dc.typeTexten_US
dcterms.creatorhttps://orcid.org/0000-0002-7280-7191

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