scholarly journals NRF2-ome: An Integrated Web Resource to Discover Protein Interaction and Regulatory Networks of NRF2

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Dénes Türei ◽  
Diána Papp ◽  
Dávid Fazekas ◽  
László Földvári-Nagy ◽  
Dezső Módos ◽  
...  

NRF2 is the master transcriptional regulator of oxidative and xenobiotic stress responses. NRF2 has important roles in carcinogenesis, inflammation, and neurodegenerative diseases. We developed an online resource, NRF2-ome, to provide an integrated and systems-level database for NRF2. The database contains manually curated and predicted interactions of NRF2 as well as data from external interaction databases. We integrated NRF2 interactome with NRF2 target genes, NRF2 regulating TFs, and miRNAs. We connected NRF2-ome to signaling pathways to allow mapping upstream NRF2 regulatory components that could directly or indirectly influence NRF2 activity totaling 35,967 protein-protein and signaling interactions. The user-friendly website allows researchers without computational background to search, browse, and download the database. The database can be downloaded in SQL, CSV, BioPAX, SBML, PSI-MI, and in a Cytoscape CYS file formats. We illustrated the applicability of the website by suggesting a posttranscriptional negative feedback of NRF2 by MAFG protein and raised the possibility of a connection between NRF2 and the JAK/STAT pathway through STAT1 and STAT3. NRF2-ome can also be used as an evaluation tool to help researchers and drug developers to understand the hidden regulatory mechanisms in the complex network of NRF2.

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7211 ◽  
Author(s):  
Roy Njoroge Kimotho ◽  
Elamin Hafiz Baillo ◽  
Zhengbin Zhang

Background Maize (Zea mays L.) is a principal cereal crop cultivated worldwide for human food, animal feed, and more recently as a source of biofuel. However, as a direct consequence of water insufficiency and climate change, frequent occurrences of both biotic and abiotic stresses have been reported in various regions around the world, and recently, this has become a constant threat in increasing global maize yields. Plants respond to abiotic stresses by utilizing the activities of transcription factors (TFs), which are families of genes coding for specific TF proteins. TF target genes form a regulon that is involved in the repression/activation of genes associated with abiotic stress responses. Therefore, it is of utmost importance to have a systematic study on each TF family, the downstream target genes they regulate, and the specific TF genes involved in multiple abiotic stress responses in maize and other staple crops. Method In this review, the main TF families, the specific TF genes and their regulons that are involved in abiotic stress regulation will be briefly discussed. Great emphasis will be given on maize abiotic stress improvement throughout this review, although other examples from different plants like rice, Arabidopsis, wheat, and barley will be used. Results We have described in detail the main TF families in maize that take part in abiotic stress responses together with their regulons. Furthermore, we have also briefly described the utilization of high-efficiency technologies in the study and characterization of TFs involved in the abiotic stress regulatory networks in plants with an emphasis on increasing maize production. Examples of these technologies include next-generation sequencing, microarray analysis, machine learning, and RNA-Seq. Conclusion In conclusion, it is expected that all the information provided in this review will in time contribute to the use of TF genes in the research, breeding, and development of new abiotic stress tolerant maize cultivars.


AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Guihua Hu ◽  
Tao Hu ◽  
Yuhua Zhan ◽  
Wei Lu ◽  
Min Lin ◽  
...  

Abstract Noncoding RNAs (ncRNAs) can finely control the expression of target genes at the posttranscriptional level in prokaryotes. Regulatory small RNAs (sRNAs) designed to control target gene expression for applications in metabolic engineering and synthetic biology have been successfully developed and used. However, the effect on the heterologous expression of species- or strain-specific ncRNAs in other bacterial strains remains poorly understood. In this work, a Pseudomonas stutzeri species-specific regulatory ncRNA, NfiS, which has been shown to play an important role in the response to oxidative stress as well as osmotic stress in P. stutzeri A1501, was cloned and transferred to the Escherichia coli strain Trans10. Recombinant NfiS-expressing E. coli, namely, Trans10-nfiS, exhibited significant enhancement of tolerance to oxidative stress. To map the possible gene regulatory networks mediated by NfiS in E. coli under oxidative stress, a microarray assay was performed to delineate the transcriptomic differences between Trans10-nfiS and wild-type E. coli under H2O2 shock treatment conditions. In all, 1184 genes were found to be significantly altered, and these genes were divided into mainly five functional categories: stress response, regulation, metabolism related, transport or membrane protein and unknown function. Our results suggest that the P. stutzeri species-specific ncRNA NfiS acts as a regulator that integrates adaptation to H2O2 with other cellular stress responses and helps protect E. coli cells against oxidative damage.


2017 ◽  
Vol 114 (51) ◽  
pp. E11037-E11046 ◽  
Author(s):  
Julieta L. Mateos ◽  
Vicky Tilmes ◽  
Pedro Madrigal ◽  
Edouard Severing ◽  
René Richter ◽  
...  

Genome-wide landscapes of transcription factor (TF) binding sites (BSs) diverge during evolution, conferring species-specific transcriptional patterns. The rate of divergence varies in different metazoan lineages but has not been widely studied in plants. We identified the BSs and assessed the effects on transcription of FLOWERING LOCUS C (FLC) and PERPETUAL FLOWERING 1 (PEP1), two orthologous MADS-box TFs that repress flowering and confer vernalization requirement in the Brassicaceae species Arabidopsis thaliana and Arabis alpina, respectively. We found that only 14% of their BSs were conserved in both species and that these contained a CArG-box that is recognized by MADS-box TFs. The CArG-box consensus at conserved BSs was extended compared with the core motif. By contrast, species-specific BSs usually lacked the CArG-box in the other species. Flowering-time genes were highly overrepresented among conserved targets, and their CArG-boxes were widely conserved among Brassicaceae species. Cold-regulated (COR) genes were also overrepresented among targets, but the cognate BSs and the identity of the regulated genes were usually different in each species. In cold, COR gene transcript levels were increased in flc and pep1-1 mutants compared with WT, and this correlated with reduced growth in pep1-1. Therefore, FLC orthologs regulate a set of conserved target genes mainly involved in reproductive development and were later independently recruited to modulate stress responses in different Brassicaceae lineages. Analysis of TF BSs in these lineages thus distinguishes widely conserved targets representing the core function of the TF from those that were recruited later in evolution.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5951 ◽  
Author(s):  
Ruijiang Li ◽  
Hebing Chen ◽  
Shuai Jiang ◽  
Wanying Li ◽  
Hao Li ◽  
...  

Transcription factors (TFs) and microRNAs (miRNAs) are well-characterized trans-acting essential players in gene expression regulation. Growing evidence indicates that TFs and miRNAs can work cooperatively, and their dysregulation has been associated with many diseases including cancer. A unified picture of regulatory interactions of these regulators and their joint target genes would shed light on cancer studies. Although online resources developed to support probing of TF-gene and miRNA-gene interactions are available, online applications for miRNA-TF co-regulatory analysis, especially with a focus on cancers, are lacking. In light of this, we developed a web tool, namely CMTCN (freely available at http://www.cbportal.org/CMTCN), which constructs miRNA-TF co-regulatory networks and conducts comprehensive analyses within the context of particular cancer types. With its user-friendly provision of topological and functional analyses, CMTCN promises to be a reliable and indispensable web tool for biomedical studies.


2019 ◽  
Vol 18 (4) ◽  
pp. 240-254 ◽  
Author(s):  
Rajat Srivastava ◽  
Rahul Kumar

AbstractUnderstanding the molecular basis of the gene-regulatory networks underlying agronomic traits or plant responses to abiotic/biotic stresses is very important for crop improvement. In this context, transcription factors, which either singularly or in conjugation directly control the expression of many target genes, are suitable candidates for improving agronomic traits via genetic engineering. In this regard, members of one of the largest class of plant-specific APETALA2/Ethylene Response Factor (AP2/ERF) superfamily, which is implicated in various aspects of development and plant stress adaptation responses, are considered high-value targets for crop improvement. Besides their long-known regulatory roles in mediating plant responses to abiotic stresses such as drought and submergence, the novel roles of AP2/ERFs during fruit ripening or secondary metabolites production have also recently emerged. The astounding functional plasticity of AP2/ERF members is considered to be achieved by their interplay with other regulatory networks and signalling pathways. In this review, we have integrated the recently accumulated evidence from functional genomics studies and described their newly emerged functions in plants. The key structural features of AP2/ERF proteins and the modes of their action are briefly summarized. The importance of AP2/ERFs in plant development and stress responses and a summary of the event of their successful applications in crop improvement programs are also provided. Altogether, we envisage that the synthesized information presented in this review will be useful to design effective strategies for improving agronomic traits in crop plants.


Microbiology ◽  
2011 ◽  
Vol 157 (3) ◽  
pp. 747-759 ◽  
Author(s):  
Chaoguang Tian ◽  
Jingyi Li ◽  
N. Louise Glass

Transcription factors (TFs) are key nodes of regulatory networks in eukaryotic organisms, including filamentous fungi such as Neurospora crassa. The 178 predicted DNA-binding TFs in N. crassa are distributed primarily among six gene families, which represent an ancient expansion in filamentous ascomycete genomes; 98 TF genes show detectable expression levels during vegetative growth of N. crassa, including 35 that show a significant difference in expression level between hyphae at the periphery versus hyphae in the interior of a colony. Regulatory networks within a species genome include paralogous TFs and their respective target genes (TF regulon). To investigate TF network evolution in N. crassa, we focused on the basic leucine zipper (bZIP) TF family, which contains nine members. We performed baseline transcriptional profiling during vegetative growth of the wild-type and seven isogenic, viable bZIP deletion mutants. We further characterized the regulatory network of one member of the bZIP family, NCU03905. NCU03905 encodes an Ap1-like protein (NcAp-1), which is involved in resistance to multiple stress responses, including oxidative and heavy metal stress. Relocalization of NcAp-1 from the cytoplasm to the nucleus was associated with exposure to stress. A comparison of the NcAp-1 regulon with Ap1-like regulons in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans and Aspergillus fumigatus showed both conservation and divergence. These data indicate how N. crassa responds to stress and provide information on pathway evolution.


2019 ◽  
Vol 20 (15) ◽  
pp. 3766 ◽  
Author(s):  
Kalaivani Nadarajah ◽  
Ilakiya Sharanee Kumar

As a semi-aquatic plant, rice requires water for proper growth, development, and orientation of physiological processes. Stress is induced at the cellular and molecular level when rice is exposed to drought or periods of low water availability. Plants have existing defense mechanisms in planta that respond to stress. In this review we examine the role played by miRNAs in the regulation and control of drought stress in rice through a summary of molecular studies conducted on miRNAs with emphasis on their contribution to drought regulatory networks in comparison to other plant systems. The interaction between miRNAs, target genes, transcription factors and their respective roles in drought-induced stresses is elaborated. The cross talk involved in controlling drought stress responses through the up and down regulation of targets encoding regulatory and functional proteins is highlighted. The information contained herein can further be explored to identify targets for crop improvement in the future.


2021 ◽  
Vol 9 (7) ◽  
pp. 1463
Author(s):  
Tamirat Tefera Temesgen ◽  
Kristoffer Relling Tysnes ◽  
Lucy Jane Robertson

Cryptosporidium oocysts are known for being very robust, and their prolonged survival in the environment has resulted in outbreaks of cryptosporidiosis associated with the consumption of contaminated water or food. Although inactivation methods used for drinking water treatment, such as UV irradiation, can inactivate Cryptosporidium oocysts, they are not necessarily suitable for use with other environmental matrices, such as food. In order to identify alternative ways to inactivate Cryptosporidium oocysts, improved methods for viability assessment are needed. Here we describe a proof of concept for a novel approach for determining how effective inactivation treatments are at killing pathogens, such as the parasite Cryptosporidium. RNA sequencing was used to identify potential up-regulated target genes induced by oxidative stress, and a reverse transcription quantitative PCR (RT-qPCR) protocol was developed to assess their up-regulation following exposure to different induction treatments. Accordingly, RT-qPCR protocols targeting thioredoxin and Cryptosporidium oocyst wall protein 7 (COWP7) genes were evaluated on mixtures of viable and inactivated oocysts, and on oocysts subjected to various potential inactivation treatments such as freezing and chlorination. The results from the present proof-of-concept experiments indicate that this could be a useful tool in efforts towards assessing potential technologies for inactivating Cryptosporidium in different environmental matrices. Furthermore, this approach could also be used for similar investigations with other pathogens.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Guiomar Martín ◽  
Yamile Márquez ◽  
Federica Mantica ◽  
Paula Duque ◽  
Manuel Irimia

Abstract Background Alternative splicing (AS) is a widespread regulatory mechanism in multicellular organisms. Numerous transcriptomic and single-gene studies in plants have investigated AS in response to specific conditions, especially environmental stress, unveiling substantial amounts of intron retention that modulate gene expression. However, a comprehensive study contrasting stress-response and tissue-specific AS patterns and directly comparing them with those of animal models is still missing. Results We generate a massive resource for Arabidopsis thaliana, PastDB, comprising AS and gene expression quantifications across tissues, development and environmental conditions, including abiotic and biotic stresses. Harmonized analysis of these datasets reveals that A. thaliana shows high levels of AS, similar to fruitflies, and that, compared to animals, disproportionately uses AS for stress responses. We identify core sets of genes regulated specifically by either AS or transcription upon stresses or among tissues, a regulatory specialization that is tightly mirrored by the genomic features of these genes. Unexpectedly, non-intron retention events, including exon skipping, are overrepresented across regulated AS sets in A. thaliana, being also largely involved in modulating gene expression through NMD and uORF inclusion. Conclusions Non-intron retention events have likely been functionally underrated in plants. AS constitutes a distinct regulatory layer controlling gene expression upon internal and external stimuli whose target genes and master regulators are hardwired at the genomic level to specifically undergo post-transcriptional regulation. Given the higher relevance of AS in the response to different stresses when compared to animals, this molecular hardwiring is likely required for a proper environmental response in A. thaliana.


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