Transcriptional rewiring of the GcrA/CcrM bacterial epigenetic regulatory system in closely related bacteria.
Transcriptional rewiring of the GcrA/CcrM bacterial epigenetic regulatory system in closely related bacteria.
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DOI：
10.1371/journal.pgen.1009433
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发表时间：
2021-03
期刊：
影响因子：
4.5
通讯作者：
Curtis PD
中科院分区：
文献类型：
--
作者：
Adhikari S;Erill I;Curtis PD
转录重连是不同生物体中不同靶基因被不同的正向调节因子调节的过程。虽然已经观察到这一现象，但尚未对其进行广泛研究，特别是在核心监管系统中。几个全球性的细胞周期调节因子在α变形菌中是保守的，为研究这一现象提供了一个很好的模型。首先在新月柄杆菌中表征，GcrA和CcrM组成了一个基于DNA甲基化的调控系统，有助于协调这种生物体的复杂生命周期。这些调节因子在α-变形菌中是非常保守的，但其调节靶点的保守程度尚不清楚。本研究利用SMRT-seq、RNA-seq和ChIP-seq技术分析了亚弧菌状短单胞菌（Brevundimonas subvibrioides）中GcrA和CcrM的调控靶点，并与其近亲C.在同一环境中生活的新月形动物虽然调控因子本身是高度保守的，但它们调控的基因却截然不同。GcrA直接调节C. crescentus，虽然B. subvibrioides与这些基因中的147个具有直系同源物，只有48个基因在其启动子区保留GcrA结合。此外，这48个基因中只有12个在gcrA突变体中表现出显著的转录变化，表明这些生物体之间存在广泛的转录重连。同样，在这些生物体中的每一个中，CcrM调节的数百个基因中，只有2个基因是共同的。当多个Alphaproteobacteria基因组进行生物信息学分析潜在的GcrA调控目标，参与DNA复制和细胞分裂的基因的调节是很好的保守在柄杆菌目，但不是在这个顺序之外。这项工作表明，显着的转录重新布线可以发生在细胞周期调控系统，即使在短的进化距离。遗传或生理系统在进化距离上的进化程度往往未经检验。我们可以假设，如果1）生物体之间的进化距离很小，2）系统执行关键功能，3）生物体处于相似的选择压力下（即生物体居住在相同的生态位），那么不同生物体中的相同系统将变化很小。Alphaproteobacteria提供了一个很好的机会来测试这一论断，因为几个关键的全球转录调节因子在整个进化枝中是保守的。在这项研究中，两个这样的全球监管机构，GcrA和CcrM，在两个密切相关的Alphaproteobacteria居住在同一生态位的调节子进行了比较，发现他们调节截然不同的基因。在许多情况下，基因存在于两种生物体中，但被一种生物体中的调节剂靶向，而不是另一种生物体。这些结果表明，即使在小的进化距离的核心调控系统中也可能发生显著的转录重布线，并表明基因和遗传调节因子的保守可能不是生物体中生理功能的完整指标。
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. 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.
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影响因子：
4.5
作者：
Fioravanti A;Fumeaux C;Mohapatra SS;Bompard C;Brilli M;Frandi A;Castric V;Villeret V;Viollier PH;Biondi EG
通讯作者：
Biondi EG
影响因子：
48
作者：
Flusberg, Benjamin A.;Webster, Dale R.;Lee, Jessica H.;Travers, Kevin J.;Olivares, Eric C.;Clark, Tyson A.;Korlach, Jonas;Turner, Stephen W.
通讯作者：
Turner, Stephen W.
影响因子：
14.9
作者：
Gonzalez D;Kozdon JB;McAdams HH;Shapiro L;Collier J
通讯作者：
Collier J
影响因子：
3.6
作者：
Curtis PD;Brun YV
通讯作者：
Brun YV
DOI：
10.1073/pnas.1319315110
发表时间：
2013-11-26
影响因子：
11.1
作者：
Kozdon, Jennifer B.;Melfi, Michael D.;McAdams, Harley H.
通讯作者：
McAdams, Harley H.