scholarly journals The polar flagellar transcriptional regulatory network in Vibrio campbellii deviates from canonical Vibrio species

2021 ◽  
Author(s):  
Blake D Petersen ◽  
Michael S Liu ◽  
Ram Podicheti ◽  
Albert Ying-Po Yang ◽  
Chelsea A Simpson ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Transcriptional Regulatory Network ◽  
Vibrio Species ◽  
Flagellar Motor ◽  
Rna Seq ◽  
Free Living ◽  
Transcriptional Regulatory ◽  
Host Mortality ◽  
Vibrio Campbellii ◽  
Fish And Shellfish

Vibrio campbellii is a Gram-negative bacterium that is free-living and ubiquitous in marine environments, and it is a pathogen of fish and shellfish. Swimming motility via a single polar flagellum is a critical virulence factor in V. campbellii pathogenesis, and disruption of the flagellar motor significantly decreases host mortality. To examine V. campbellii flagellar gene regulation, we identified homologs of flagellar and chemotaxis genes conserved in other members of the Vibrionaceae and determined the transcriptional profile of these loci using differential RNA-seq. We systematically deleted all 63 predicted flagellar and chemotaxis genes in V. campbellii and examined their effects on motility and flagellum production. We specifically focused on the core flagellar regulators of the flagellar regulatory hierarchy established in other Vibrios: RpoN (σ54), FlrA, FlrC, and FliA. Our results show that V. campbellii transcription of flagellar and chemotaxis genes is governed by a multi-tiered regulatory hierarchy similar to other motile Vibrio species but with two critical differences: the σ54-dependent regulator FlrA is dispensable for motility, and Class II gene expression is independent of σ54 regulation. Our genetic and phenotypic dissection of the V. campbellii flagellar regulatory network highlights the differences that have evolved in flagellar regulation across the Vibrionaceae.

scholarly journals The polar flagellar transcriptional regulatory network in Vibrio campbellii deviates from canonical Vibrio species

2021 ◽  
Author(s):  
Blake D. Petersen ◽  
Michael S. Liu ◽  
Ram Podicheti ◽  
Albert Ying-Po Yang ◽  
Chelsea A. Simpson ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Regulatory Network ◽  
Transcriptional Regulatory Network ◽  
Model Organism ◽  
Key Factor ◽  
Host Mortality ◽  
And Function ◽  
Vibrio Campbellii ◽  
Fish And Shellfish ◽  
The Impact

Swimming motility is a critical virulence factor in pathogenesis for numerous Vibrio species. Vibrio campbellii DS40M4 is a wild isolate that has been recently established as a highly tractable model strain for bacterial genetics studies. We sought to exploit the tractability and relevance of this strain for characterization of flagellar gene regulation in V. campbellii . Using comparative genomics, we identified homologs of V. campbellii flagellar and chemotaxis genes conserved in other members of the Vibrionaceae and determined the transcriptional profile of these loci using differential RNA-seq. We systematically deleted all 63 predicted flagellar and chemotaxis genes in V. campbellii and examined their effects on motility and flagellum production. We specifically focused on the core regulators of the flagellar hierarchy established in other vibrios: RpoN (σ 54 ), FlrA, FlrC, and FliA. Our results show that V. campbellii transcription of flagellar and chemotaxis genes is governed by a multi-tiered regulatory hierarchy similar to other motile Vibrio species. However, there are several critical differences in V. campbellii : (i) the σ 54 -dependent regulator FlrA is dispensable for motility, (ii) the flgA , fliEFGHIJ , flrA , and flrBC operons do not require σ 54 for expression, and (iii) FlrA and FlrC co-regulate class II genes. Our model proposes that the V. campbellii flagellar transcriptional hierarchy has three classes of genes, in contrast to the four-class hierarchy in Vibrio cholerae . Our genetic and phenotypic dissection of the V. campbellii flagellar regulatory network highlights the differences that have evolved in flagellar regulation across the Vibrionaceae. Importance Vibrio campbellii is a Gram-negative bacterium that is free-living and ubiquitous in marine environments and is an important global pathogen of fish and shellfish. Disruption of the flagellar motor significantly decreases host mortality of V. campbellii , suggesting that motility is a key factor in pathogenesis. Using this model organism, we identified >60 genes that encode proteins with predicted structural, mechanical, or regulatory roles in function of the single polar flagellum in V. campbellii . We systematically tested strains containing single deletions of each gene to determine the impact on motility and flagellum production. Our studies have uncovered differences in the regulatory network and function of several genes in V. campbellii as compared to established systems in Vibrio cholerae and Vibrio parahaemolyticus .

scholarly journals Single-Cell Transcriptomics-Based Study of Transcriptional Regulatory Features in the Mouse Brain Vasculature

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Wei-Wei Lin ◽  
Lin-Tao Xu ◽  
Yi-Sheng Chen ◽  
Ken Go ◽  
Chenyu Sun ◽  
...  
Keyword(s):  
Single Cell ◽  
Mouse Brain ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Network ◽  
Rna Seq ◽  
Brain Vasculature ◽  
Transcriptional Regulatory ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Background. The critical role of vascular health on brain function has received much attention in recent years. At the single-cell level, studies on the developmental processes of cerebral vascular growth are still relatively few. Techniques for constructing gene regulatory networks (GRNs) based on single-cell transcriptome expression data have made significant progress in recent years. Herein, we constructed a single-cell transcriptional regulatory network of mouse cerebrovascular cells. Methods. The single-cell RNA-seq dataset of mouse brain vessels was downloaded from GEO (GSE98816). This cell clustering was annotated separately using singleR and CellMarker. We then used a modified version of the SCENIC method to construct GRNs. Next, we used a mouse version of SEEK to assess whether genes in the regulon were coexpressed. Finally, regulatory module analysis was performed to complete the cell type relationship quantification. Results. Single-cell RNA-seq data were used to analyze the heterogeneity of mouse cerebrovascular cells, whereby four cell types including endothelial cells, fibroblasts, microglia, and oligodendrocytes were defined. These subpopulations of cells and marker genes together characterize the molecular profile of mouse cerebrovascular cells. Through these signatures, key transcriptional regulators that maintain cell identity were identified. Our findings identified genes like Lmo2, which play an important role in endothelial cells. The same cell type, for instance, fibroblasts, was found to have different regulatory networks, which may influence the functional characteristics of local tissues. Conclusions. In this study, a transcriptional regulatory network based on single-cell analysis was constructed. Additionally, the study identified and profiled mouse cerebrovascular cells using single-cell transcriptome data as well as defined TFs that affect the regulatory network of the mouse brain vasculature.

scholarly journals Topological and causal structure of the yeast transcriptional regulatory network

10.1038/ng873 ◽  
2002 ◽  
Vol 31 (1) ◽  
pp. 60-63 ◽  
Author(s):  
Nabil Guelzim ◽  
Samuele Bottani ◽  
Paul Bourgine ◽  
François Képès
Keyword(s):  
Regulatory Network ◽  
Transcriptional Regulatory Network ◽  
Causal Structure ◽  
Transcriptional Regulatory

scholarly journals Screening Driving Transcription Factors in the Processing of Gastric Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Guangzhong Xu ◽  
Kai Li ◽  
Nengwei Zhang ◽  
Bin Zhu ◽  
Guosheng Feng
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
Regulatory Network ◽  
Target Genes ◽  
Transcriptional Regulatory Network ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Regulatory Mechanisms ◽  
Integrated Analysis ◽  
Transcriptional Regulatory

Background. Construction of the transcriptional regulatory network can provide additional clues on the regulatory mechanisms and therapeutic applications in gastric cancer.Methods. Gene expression profiles of gastric cancer were downloaded from GEO database for integrated analysis. All of DEGs were analyzed by GO enrichment and KEGG pathway enrichment. Transcription factors were further identified and then a global transcriptional regulatory network was constructed.Results. By integrated analysis of the six eligible datasets (340 cases and 43 controls), a bunch of 2327 DEGs were identified, including 2100 upregulated and 227 downregulated DEGs. Functional enrichment analysis of DEGs showed that digestion was a significantly enriched GO term for biological process. Moreover, there were two important enriched KEGG pathways: cell cycle and homologous recombination. Furthermore, a total of 70 differentially expressed TFs were identified and the transcriptional regulatory network was constructed, which consisted of 566 TF-target interactions. The top ten TFs regulating most downstream target genes were BRCA1, ARID3A, EHF, SOX10, ZNF263, FOXL1, FEV, GATA3, FOXC1, and FOXD1. Most of them were involved in the carcinogenesis of gastric cancer.Conclusion. The transcriptional regulatory network can help researchers to further clarify the underlying regulatory mechanisms of gastric cancer tumorigenesis.

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