Functional Role of Aspergillus carbonarius AcOTAbZIP Gene, a bZIP Transcription Factor within the OTA Gene Cluster

Aspergillus carbonarius is the principal fungal species responsible for ochratoxin A (OTA) contamination of grapes and derived products in the main viticultural regions worldwide. In recent years, co-expressed genes representing a putative-OTA gene cluster were identified, and the deletion of a few of them allowed the partial elucidation of the biosynthetic pathway in the fungus. In the putative OTA-gene cluster is additionally present a bZIP transcription factor (AcOTAbZIP), and with this work, A. carbonarius ΔAcOTAbZIP strains were generated to study its functional role. According to phylogenetic analysis, the gene is conserved in the OTA-producing fungi. A Saccharomyces cerevisiae transcription factor binding motif (TFBM) homolog, associated with bZIP transcription factors was present in the A. carbonarius OTA-gene cluster no-coding regions. AcOTAbZIP deletion results in the loss of OTA and the intermediates OTB and OTβ. Additionally, in ΔAcOTAbZIP strains, a down-regulation of AcOTApks, AcOTAnrps, AcOTAp450, and AcOTAhal genes was observed compared to wild type (WT). These results provide evidence of the direct involvement of the AcOTAbZIP gene in the OTA biosynthetic pathway by regulating the involved genes. The loss of OTA biosynthesis ability does not affect fungal development as demonstrated by the comparison of ΔAcOTAbZIP strains and WT strains in terms of vegetative growth and asexual sporulation on three different media. Finally, no statistically significant differences in virulence were observed among ΔAcOTAbZIP strains and WT strains on artificially inoculated grape berries, demonstrating that OTA is not required by A. carbonarius for the pathogenicity process.

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A combinatorial action of GmMYB176 and GmbZIP5 controls isoflavonoid biosynthesis in soybean (Glycine max)

Communications Biology ◽

10.1038/s42003-021-01889-6 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Arun Kumaran Anguraj Vadivel ◽

Tim McDowell ◽

Justin B. Renaud ◽

Sangeeta Dhaubhadel

Keyword(s):

Transcription Factor ◽

Hairy Roots ◽

Defense Mechanisms ◽

Biosynthetic Pathway ◽

Bzip Transcription Factor ◽

Myb Transcription Factor ◽

In Planta ◽

Rnai Silencing ◽

Protein Protein Interaction ◽

Soybean Roots

AbstractGmMYB176 is an R1 MYB transcription factor that regulates multiple genes in the isoflavonoid biosynthetic pathway, thereby affecting their levels in soybean roots. While GmMYB176 is important for isoflavonoid synthesis, it is not sufficient for the function and requires additional cofactor(s). The aim of this study was to identify the GmMYB176 interactome for the regulation of isoflavonoid biosynthesis in soybean. Here, we demonstrate that a bZIP transcription factor GmbZIP5 co-immunoprecipitates with GmMYB176 and shows protein–protein interaction in planta. RNAi silencing of GmbZIP5 reduced the isoflavonoid level in soybean hairy roots. Furthermore, co-overexpression of GmMYB176 and GmbZIP5 enhanced the level of multiple isoflavonoid phytoallexins including glyceollin, isowighteone and a unique O-methylhydroxy isoflavone in soybean hairy roots. These findings could be utilized to develop biotechnological strategies to manipulate the metabolite levels either to enhance plant defense mechanisms or for human health benefits in soybean or other economically important crops.

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Transcription Factor Binding Motif (TFBM)

Dictionary of Bioinformatics and Computational Biology ◽

10.1002/9780471650126.dob1114 ◽

2004 ◽

Author(s):

Jacques van Helden

Keyword(s):

Transcription Factor ◽

Transcription Factor Binding ◽

Binding Motif ◽

Transcription Factor Binding Motif ◽

Factor Binding

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Genome-wide association between transcription factor expression and chromatin accessibility reveals chromatin state regulators

10.1101/043414 ◽

2016 ◽

Author(s):

David Felix Lamparter ◽

Daniel Marbach ◽

Rico Rueedi ◽

Sven Bergmann ◽

Zoltan Kutalik

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Chromatin Accessibility ◽

Binding Motif ◽

Open Chromatin ◽

Data Sets ◽

Transcription Factor Binding Motif ◽

Data Set ◽

Data Driven Approach ◽

Transcription Factor Expression

To better understand genome regulation, it is important to uncover the role of transcription factors in the process of chromatin structure establishment and maintenance. Here we present a data-driven approach to systematically characterize transcription factors that are relevant for this process. Our method uses a linear mixed modeling approach to combine data sets of transcription factor binding motif enrichments in open chromatin and gene expression across the same set of cell lines. Applying this approach to the ENCODE data set we confirm already known and imply numerous novel transcription factors in playing a role in the establishment or maintenance of open chromatin.

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RSAT matrix-clustering: dynamic exploration and redundancy reduction of transcription factor binding motif collections

10.1101/065565 ◽

2016 ◽

Cited By ~ 1

Author(s):

Jaime Abraham Castro-Mondragon ◽

Sébastien Jaeger ◽

Denis Thieffry ◽

Morgane Thomas-Chollier ◽

Jacques van Helden

Keyword(s):

Transcription Factor ◽

Motif Discovery ◽

Binding Motif ◽

Data Sets ◽

Transcription Factor Binding Motif ◽

Biologically Relevant ◽

Manual Curation ◽

Versatile Tool ◽

Multiple Motif ◽

Multiple Trees

ABSTRACTTranscription Factor (TF) databases contain multitudes of motifs from various sources, from which non-redundant collections are derived by manual curation. The advent of high-throughput methods stimulated the production of novel collections with increasing numbers of motifs. Meta-databases, built by merging these collections, contain redundant versions, because available tools are not suited to automatically identify and explore biologically relevant clusters among thousands of motifs. Motif discovery from genome-scale data sets (e.g. ChIP-seq peaks) also produces redundant motifs, hampering the interpretation of results. We present matrix-clustering, a versatile tool that clusters similar TFBMs into multiple trees, and automatically creates non-redundant collections of motifs. A feature unique to matrix-clustering is its dynamic visualisation of aligned TFBMs, and its capability to simultaneously treat multiple collections from various sources. We demonstrate that matrix-clustering considerably simplifies the interpretation of combined results from multiple motif discovery tools and highlights biologically relevant variations of similar motifs. By clustering 24 entire databases (>7,500 motifs), we show that matrix-clustering correctly groups motifs belonging to the same TF families, and can drastically reduce motif redundancy. matrix-clustering is integrated within the RSAT suite (http://rsat.eu/), accessible through a user-friendly web interface or command-line for its integration in pipelines.

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Activity of Cordycepin From Cordyceps sinensis Against Drug-Resistant Tumor Cells as Determined by Gene Expression and Drug Sensitivity Profiling

Natural Product Communications ◽

10.1177/1934578x21993350 ◽

2021 ◽

Vol 16 (2) ◽

pp. 1934578X2199335

Author(s):

Nadire Özenver ◽

Joelle C. Boulos ◽

Thomas Efferth

Keyword(s):

Transcription Factor ◽

Drug Sensitivity ◽

Experimental Studies ◽

Cordyceps Sinensis ◽

Parasitic Fungus ◽

Cross Resistance ◽

Binding Motif ◽

Tumor Type ◽

Transcription Factor Binding Motif

Cordycepin is one of the substantial components of the parasitic fungus Cordyceps sinensis as well as other Cordyceps species. It exerts various effects such as antimetastatic, antiinflammatory, antioxidant, and neuroprotective activities. Assorted studies revealed in vitro and in vivo anticancer influence of cordycepin and put forward its potential for cancer therapy. However, the role of multidrug resistance-associated mechanisms for the antitumor effect of cordycepin has not been investigated in great detail thus far. Therefore, we searched cordycepin’s cytotoxicity with regard to well-known anticancer drug resistance mechanisms, including ABCB1, ABCB5, ABCC1, ABCG2, EGFR, and TP53, and identified putative molecular determinants related to the cellular responsiveness of cordycepin. Bioinformatic analyses of NCI microarray data and gene promoter transcription factor binding motif analyses were performed to specify the mechanisms of cordycepin towards cancer cells. COMPARE and hierarchical analyses led to the detection of the genes involved in cordycepin’s cytotoxicity and sensitivity and resistance of cell lines towards cordycepin. Tumor-type dependent response and cross-resistance profiles were further unravelled. We found transcription factors potentially involved in the common transcriptional regulation of the genes identified by COMPARE analyses. Cordycepin bypassed resistance mediated by the expression of ATP-binding cassete (ABC) transporters (P-gp, ABCB5, ABCC1 and BCRP) and mutant epidermal growth factor receptor (EGFR). The drug sensitivity profiles of several DNA Topo I and II inhibitors were significantly correlated with those of cordycepin’s activity. Among eight different tumor types, prostate cancer was the most sensitive, whereas renal carcinoma was the most resistant to cordycepin. NF-κB was discovered as a common transcription factor. The potential of cordycepin is set forth as a potential new drug lead by bioinformatic evaluations. Further experimental studies are warranted for better understanding of cordycepin’s activity against cancer.

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Rational gRNA Design Based on Transcription Factor Binding Data

Synthetic Biology ◽

10.1093/synbio/ysab014 ◽

2021 ◽

Author(s):

David Bergenholm ◽

Yasaman Dabirian ◽

Raphael Ferreira ◽

Verena Siewers ◽

Florian David ◽

...

Keyword(s):

Transcription Factor ◽

Genome Engineering ◽

Transcription Factor Binding ◽

Central Carbon Metabolism ◽

Binding Motif ◽

Transcription Factor Binding Motif ◽

Factor Binding ◽

Transcription Factor Motif ◽

Binding Data ◽

Genes Encoding

Abstract The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system has become a standard tool in many genome engineering endeavors. The endonuclease-deficient version of Cas9 (dCas9) is also a powerful programmable tool for gene regulation. In this study, we made use of Saccharomyces cerevisiae transcription factor binding data to obtain a better understanding of the interplay between transcription factor binding and binding of dCas9 fused to an activator domain, VPR. More specifically, we targeted dCas9-VPR towards binding sites of Gcr1-Gcr2 and Tye7 present in several promoters of genes encoding enzymes engaged in the central carbon metabolism. From our data, we observed an upregulation of gene expression when dCas9-VPR was targeted next to a transcription factor binding motif, whereas downregulation or no change was observed when dCas9 was bound on a transcription factor motif. This suggests a steric competition between dCas9 and the specific transcription factor. Integrating transcription factor binding data, therefore, proved to be useful for designing gRNAs for CRISPRi/a applications.

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