scholarly journals MarR Family Transcription Factors fromBurkholderiaSpecies: Hidden Clues to Control of Virulence-Associated Genes

2018 ◽  
Vol 83 (1) ◽  
Author(s):  
Ashish Gupta ◽  
Anuja Pande ◽  
Afsana Sabrin ◽  
Sudarshan S. Thapa ◽  
Brennan W. Gioe ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Environmental Changes ◽  
Phenotypic Diversity ◽  
Regulation Of Gene Expression ◽  
Virulence Determinants ◽  
Human Pathogens ◽  
Plant Host ◽  
Gene Regulatory

SUMMARYSpecies within the genusBurkholderiaexhibit remarkable phenotypic diversity. Genomic plasticity, including genome reduction and horizontal gene transfer, has been correlated with virulence traits in several species. However, the conservation of virulence genes in species otherwise considered to have limited potential for infection suggests that phenotypic diversity may not be explained solely on the basis of genetic diversity. Instead, differential organization and control of gene regulatory networks may underlie many phenotypic differences. In this review, we evaluate how regulation of gene expression by members of the multiple antibiotic resistance regulator (MarR) family of transcription factors may contribute to shaping the physiological diversity ofBurkholderiaspecies, with a focus on the clinically relevant human pathogens. AllBurkholderiaspecies encode a relatively large number of MarR proteins, a feature common to bacteria that must respond to environmental changes such as those associated with host invasion. However, evolution of gene regulatory networks has likely resulted in orthologous transcription factors controlling disparate sets of genes. Adaptation to, and survival in, diverse habitats, including a human or plant host, is key to the success ofBurkholderiaspecies as (opportunistic) pathogens, and recent reports suggest that control of virulence-associated genes by MarR proteins features prominently among the survival strategies employed by these species. We suggest that identification of MarR regulons will contribute significantly to clarification of virulence determinants and phenotypic diversity.

scholarly journals Identifying genetic modulators of the connectivity between transcription factors and their transcriptional targets

2016 ◽  
Vol 113 (13) ◽  
pp. E1835-E1843 ◽  
Author(s):  
Mina Fazlollahi ◽  
Ivor Muroff ◽  
Eunjee Lee ◽  
Helen C. Causton ◽  
Harmen J. Bussemaker
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Nonsynonymous Mutation ◽  
Gene Regulatory ◽  
Genetic Modulators

Regulation of gene expression by transcription factors (TFs) is highly dependent on genetic background and interactions with cofactors. Identifying specific context factors is a major challenge that requires new approaches. Here we show that exploiting natural variation is a potent strategy for probing functional interactions within gene regulatory networks. We developed an algorithm to identify genetic polymorphisms that modulate the regulatory connectivity between specific transcription factors and their target genes in vivo. As a proof of principle, we mapped connectivity quantitative trait loci (cQTLs) using parallel genotype and gene expression data for segregants from a cross between two strains of the yeast Saccharomyces cerevisiae. We identified a nonsynonymous mutation in the DIG2 gene as a cQTL for the transcription factor Ste12p and confirmed this prediction empirically. We also identified three polymorphisms in TAF13 as putative modulators of regulation by Gcn4p. Our method has potential for revealing how genetic differences among individuals influence gene regulatory networks in any organism for which gene expression and genotype data are available along with information on binding preferences for transcription factors.

scholarly journals Automated generation of context-specific Gene Regulatory Networks with a weighted approach in D. melanogaster

2020 ◽  
Author(s):  
Leandro Murgas ◽  
Sebastian Contreras-Riquelme ◽  
J. Eduardo Martínez ◽  
Camilo Villaman ◽  
Rodrigo Santibáñez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Chromatin Accessibility ◽  
Reference Network ◽  
Specific Gene ◽  
Gene Regulatory

AbstractMotivationThe regulation of gene expression is a key factor in the development and maintenance of life in all organisms. This process is carried out mainly through the action of transcription factors (TFs), although other actors such as ncRNAs are involved. In this work, we propose a new method to construct Gene Regulatory Networks (GRNs) depicting regulatory events in a certain context for Drosophila melanogaster. Our approach is based on known relationships between epigenetics and the activity of transcription factors.ResultsWe developed method, Tool for Weighted Epigenomic Networks in D. melanogaster (Fly T-WEoN), which generates GRNs starting from a reference network that contains all known gene regulations in the fly. Regulations that are unlikely taking place are removed by applying a series of knowledge-based filters. Each of these filters is implemented as an independent module that considers a type of experimental evidence, including DNA methylation, chromatin accessibility, histone modifications, and gene expression. Fly T-WEoN is based on heuristic rules that reflect current knowledge on gene regulation in D. melanogaster obtained from literature. Experimental data files can be generated with several standard procedures and used solely when and if available.Fly T-WEoN is available as a Cytoscape application that permits integration with other tools, and facilitates downstream network analysis. In this work, we first demonstrate the reliability of our method to then provide a relevant application case of our tool: early development of D. melanogaster.AvailabilityFly T-WEoN, together with its step-by-step guide is available at https://[email protected]

Regulation of gene expression in the nervous system

2008 ◽  
Vol 414 (3) ◽  
pp. 327-341 ◽  
Author(s):  
Lezanne Ooi ◽  
Ian C. Wood
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Gene Regulatory

The nervous system contains a multitude of cell types which are specified during development by cascades of transcription factors acting combinatorially. Some of these transcription factors are only active during development, whereas others continue to function in the mature nervous system to maintain appropriate gene-expression patterns in differentiated cells. Underpinning the function of the nervous system is its plasticity in response to external stimuli, and many transcription factors are involved in regulating gene expression in response to neuronal activity, allowing us to learn, remember and make complex decisions. Here we review some of the recent findings that have uncovered the molecular mechanisms that underpin the control of gene regulatory networks within the nervous system. We highlight some recent insights into the gene-regulatory circuits in the development and differentiation of cells within the nervous system and discuss some of the mechanisms by which synaptic transmission influences transcription-factor activity in the mature nervous system. Mutations in genes that are important in epigenetic regulation (by influencing DNA methylation and post-translational histone modifications) have long been associated with neuronal disorders in humans such as Rett syndrome, Huntington's disease and some forms of mental retardation, and recent work has focused on unravelling their mechanisms of action. Finally, the discovery of microRNAs has produced a paradigm shift in gene expression, and we provide some examples and discuss the contribution of microRNAs to maintaining dynamic gene regulatory networks in the brain.

scholarly journals Upregulation and cell specificity of C4 genes are derived from ancestral C3 gene regulatory networks

2020 ◽  
Author(s):  
Pallavi Singh ◽  
Sean R. Stevenson ◽  
Ivan Reyna-Llorens ◽  
Gregory Reeves ◽  
Tina B. Schreier ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Transcript Accumulation ◽  
Specific Expression ◽  
Cell Specificity ◽  
Distinct Cell ◽  
Gene Regulatory

ABSTRACTThe efficient C4 pathway is based on strong up-regulation of genes found in C3 plants, but also compartmentation of their expression into distinct cell-types such as the mesophyll and bundle sheath. Transcription factors associated with these phenomena have not been identified. To address this, we undertook genome-wide analysis of transcript accumulation, chromatin accessibility and transcription factor binding in C4Gynandropsis gynandra. From these data, two models relating to the molecular evolution of C4 photosynthesis are proposed. First, increased expression of C4 genes is associated with increased binding by MYB-related transcription factors. Second, mesophyll specific expression is associated with binding of homeodomain transcription factors. Overall, we conclude that during evolution of the complex C4 trait, C4 cycle genes gain cis-elements that operate in the C3 leaf such that they become integrated into existing gene regulatory networks associated with cell specificity and photosynthesis.

scholarly journals Revealing the Key Regulators of Cell Identity in the Human Adult Pancreas

2020 ◽  
Author(s):  
Lotte Vanheer ◽  
Andrea Alex Schiavo ◽  
Matthias Van Haele ◽  
Tine Haesen ◽  
Adrian Janiszewski ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Types ◽  
List Type ◽  
Cell Identity ◽  
Pancreatic Cell ◽  
Human Adult ◽  
Gene Regulatory ◽  
Cellular Identity

SUMMARYCellular identity during development is under the control of transcription factors that form gene regulatory networks. However, the transcription factors and gene regulatory networks underlying cellular identity in the human adult pancreas remain largely unexplored. Here, we integrate multiple single-cell RNA sequencing datasets of the human adult pancreas, totaling 7393 cells, and comprehensively reconstruct gene regulatory networks. We show that a network of 142 transcription factors forms distinct regulatory modules that characterize pancreatic cell types. We present evidence that our approach identifies key regulators of cell identity in the human adult pancreas. We predict that HEYL and JUND are active in acinar and alpha cells, respectively, and show that these proteins are present in the human adult pancreas as well as in human induced pluripotent stem cell-derived pancreatic cells. The comprehensive gene regulatory network atlas can be explored interactively online. We anticipate our analysis to be the starting point for a more sophisticated dissection of how transcription factors regulate cell identity in the human adult pancreas. Furthermore, given that transcription factors are major regulators of embryo development and are often perturbed in diseases, a comprehensive understanding of how transcription factors work will be relevant in development and disease biology.HIGHLIGHTS-Reconstruction of gene regulatory networks for human adult pancreatic cell types-An interactive resource to explore and visualize gene expression and regulatory states-Predicting putative transcription factors driving pancreatic cell identity-HEYL and JUND as candidate regulators of acinar and alpha cell identity, respectively

scholarly journals Cell-free gene-regulatory network engineering with synthetic transcription factors

2019 ◽  
Vol 116 (13) ◽  
pp. 5892-5901 ◽  
Author(s):  
Zoe Swank ◽  
Nadanai Laohakunakorn ◽  
Sebastian J. Maerkl
Keyword(s):  
Transcription Factors ◽  
High Throughput ◽  
Gene Regulatory Networks ◽  
Protein Interactions ◽  
Transcriptional Repression ◽  
Regulatory Networks ◽  
De Novo ◽  
Mechanistic Modeling ◽  
Free System ◽  
Gene Regulatory

Gene-regulatory networks are ubiquitous in nature and critical for bottom-up engineering of synthetic networks. Transcriptional repression is a fundamental function that can be tuned at the level of DNA, protein, and cooperative protein–protein interactions, necessitating high-throughput experimental approaches for in-depth characterization. Here, we used a cell-free system in combination with a high-throughput microfluidic device to comprehensively study the different tuning mechanisms of a synthetic zinc-finger repressor library, whose affinity and cooperativity can be rationally engineered. The device is integrated into a comprehensive workflow that includes determination of transcription-factor binding-energy landscapes and mechanistic modeling, enabling us to generate a library of well-characterized synthetic transcription factors and corresponding promoters, which we then used to build gene-regulatory networks de novo. The well-characterized synthetic parts and insights gained should be useful for rationally engineering gene-regulatory networks and for studying the biophysics of transcriptional regulation.

scholarly journals Randomization Strategies Affect Motif Significance Analysis in TF-miRNA-Gene Regulatory Networks

2017 ◽  
Vol 14 (2) ◽  
Author(s):  
Sepideh Sadegh ◽  
Maryam Nazarieh ◽  
Christian Spaniol ◽  
Volkhard Helms
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Degree Distribution ◽  
Regulatory Networks ◽  
Target Genes ◽  
Mirna Gene ◽  
Biological Cells ◽  
Significance Analysis ◽  
Gene Regulatory ◽  
Randomized Networks

AbstractGene-regulatory networks are an abstract way of capturing the regulatory connectivity between transcription factors, microRNAs, and target genes in biological cells. Here, we address the problem of identifying enriched co-regulatory three-node motifs that are found significantly more often in real network than in randomized networks. First, we compare two randomization strategies, that either only conserve the degree distribution of the nodes’ in- and out-links, or that also conserve the degree distributions of different regulatory edge types. Then, we address the issue how convergence of randomization can be measured. We show that after at most 10 × |E| edge swappings, converged motif counts are obtained and the memory of initial edge identities is lost.

scholarly journals An Integrated Database of Small RNAs and Their Interplay With Transcriptional Gene Regulatory Networks in Corynebacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Mariana Teixeira Dornelles Parise ◽  
Doglas Parise ◽  
Flavia Figueira Aburjaile ◽  
Anne Cybelle Pinto Gomide ◽  
Rodrigo Bentes Kato ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Small Rnas ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Bacterial Gene ◽  
Bacterial Gene Expression ◽  
Transcriptional Regulatory ◽  
Animal Pathogens ◽  
Gene Regulatory

Small RNAs (sRNAs) are one of the key players in the post-transcriptional regulation of bacterial gene expression. These molecules, together with transcription factors, form regulatory networks and greatly influence the bacterial regulatory landscape. Little is known concerning sRNAs and their influence on the regulatory machinery in the genus Corynebacterium, despite its medical, veterinary and biotechnological importance. Here, we expand corynebacterial regulatory knowledge by integrating sRNAs and their regulatory interactions into the transcriptional regulatory networks of six corynebacterial species, covering four human and animal pathogens, and integrate this data into the CoryneRegNet database. To this end, we predicted sRNAs to regulate 754 genes, including 206 transcription factors, in corynebacterial gene regulatory networks. Amongst them, the sRNA Cd-NCTC13129-sRNA-2 is predicted to directly regulate ydfH, which indirectly regulates 66 genes, including the global regulator glxR in C. diphtheriae. All of the sRNA-enriched regulatory networks of the genus Corynebacterium have been made publicly available in the newest release of CoryneRegNet(www.exbio.wzw.tum.de/coryneregnet/) to aid in providing valuable insights and to guide future experiments.

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