scholarly journals TAL Effector Repertoires of Strains of Xanthomonas phaseoli pv. manihotis in Commercial Cassava Crops Reveal High Diversity at the Country Scale

2021 ◽  
Vol 9 (2) ◽  
pp. 315
Author(s):  
Carlos A. Zárate-Chaves ◽  
Daniela Osorio-Rodríguez ◽  
Rubén E. Mora ◽  
Álvaro L. Pérez-Quintero ◽  
Alexis Dereeper ◽  
...  
Keyword(s):  
Target Genes ◽  
Susceptibility Gene ◽  
Rflp Analysis ◽  
Transcription Activator ◽  
Cassava Bacterial Blight ◽  
Functional Convergence ◽  
Neutral Genetic Diversity ◽  
Functional Variant ◽  
Novel Variants ◽  
Host Metabolism

Transcription activator-like effectors (TALEs) play a significant role for pathogenesis in several xanthomonad pathosystems. Xanthomonas phaseoli pv. manihotis (Xpm), the causal agent of Cassava Bacterial Blight (CBB), uses TALEs to manipulate host metabolism. Information about Xpm TALEs and their target genes in cassava is scarce, but has been growing in the last few years. We aimed to characterize the TALE diversity in Colombian strains of Xpm and to screen for TALE-targeted gene candidates. We selected eighteen Xpm strains based on neutral genetic diversity at a country scale to depict the TALE diversity among isolates from cassava productive regions. RFLP analysis showed that Xpm strains carry TALomes with a bimodal size distribution, and affinity-based clustering of the sequenced TALEs condensed this variability mainly into five clusters. We report on the identification of 13 novel variants of TALEs in Xpm, as well as a functional variant with 22 repeats that activates the susceptibility gene MeSWEET10a, a previously reported target of TAL20Xam668. Transcriptomics and EBE prediction analyses resulted in the selection of several TALE-targeted candidate genes and two potential cases of functional convergence. This study provides new bases for assessing novel potential TALE targets in the Xpm–cassava interaction, which could be important factors that define the fate of the infection.

A case of rare allele T 126, 30,32 base pairs in a schizophrenic patient: A study case

2016 ◽  
Vol 33 (S1) ◽  
pp. S585-S586
Author(s):  
A.I. Sabau ◽  
P. Cristina ◽  
B. Valerica ◽  
P. Delia Marina
Keyword(s):  
Schizophrenic Patient ◽  
Complex Disease ◽  
Susceptibility Gene ◽  
Rflp Analysis ◽  
Rare Allele ◽  
Base Pairs ◽  
Gene Coding ◽  
Icd 10 ◽  
Schizophrenic Patients ◽  
Competing Interest

IntroductionSchizophrenia is a severe and complex disease clinically characterized by disturbed thought processes, delusions, hallucinations and reduced social skills. Gene coding for neregulin 1 (NRG 1) located in 8 p21chromosomeand single nucleotide polymorphism (SNPs) have been identified strongly supporting NRG1 gene as a susceptibility gene for schizophrenia.ObjectiveThe present preliminary study, determines the relationship between polymorphism nucleotide sites (SNPs2) of NRG1 gene and schizophrenia.AimsIdentifying rare allele T of neregulin 1 genein schizophrenic patients.MethodWe analyzed the polymorphism (SNPs2) of NRG1 gene in 20 patients recruited from Psychiatry Department of Emergency Clinical Hospital of Arad diagnosed with schizophrenia according to DSM-5-TM and ICD-10 criteria and 10 healthy controls. From all subjects, we obtained 2 mL of peripheral blood samples. Genomic DNA was extracted using the phenol-chloroform method. Genotyping was performed byPCR-based RFLP analysis for all subjects. The obtained PCR product mixture was completely digested with restriction enzyme, separated on SNP1 and SNP2 agarose gel. We present the case of a 31 years old, male, schizophrenic patient with the SNPs2 polymorphism and rare allele T 126.ResultsIn both groups, common allele G 127 and 60 base pairs was identified but only 2 schizophrenic patients presented rare allele T 126 and 30,32 base pairs.ConclusionsThe polymorphism SNPs2 of NRG1 gene with rare allele T 126 and 30,32 base pairs, may play a role in predisposing an individual to schizophrenia. Further and extended replicating studies with multiple sequencing of NRG1 gene are necessary.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Suppression of the rbf null mutants by a de2f1 allele that lacks transactivation domain

Development ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 367-379 ◽  
Author(s):  
W. Du
Keyword(s):  
Cell Proliferation ◽  
Target Genes ◽  
Suppressor Gene ◽  
Genetic Interactions ◽  
Transactivation Domain ◽  
Transcription Activator ◽  
Drosophila Development ◽  
Mitotic Wave ◽  
E2f Transcription Factors ◽  
Null Mutants

In mammals, a large number of proteins including E2F transcription factors have been shown to interact with the tumor suppressor gene product pRB, but it is not clear to what extend the function of pRB is mediated by E2F. In addition, E2F was shown to mediate both transcription activation and repression; it remains to be tested which function of E2F is critical for normal development. Drosophila homologs of the RB and E2F family of proteins RBF and dE2F1 have been identified. The genetic interactions between rbf and de2f1 were analyzed during Drosophila development, and the results presented here showed that RBF is required at multiple stages of development. Unexpectedly, rbf null mutants can develop until late pupae stage when the activity of dE2F1 is reduced, and can develop into viable adults with normal adult appendages in the presence of a de2f1 mutation that retains the DNA binding domain but lacks the transactivation domain. These results indicate that most, if not all, of the function of RBF during development is mediated through E2F. In turn, the genetic interactions shown here also suggest that dE2F1 functions primarily as a transcription activator rather than a co-repressor of RBF during Drosophila development. Analysis of the expression of an E2F target gene PCNA in eye discs showed that the expression of PCNA is activated by dE2F1 in the second mitotic wave and repressed in the morphogenetic furrow and posterior to the second mitotic wave by RBF. Interestingly, reducing the level of RBF restored the normal pattern of cell proliferation in de2f1 mutant eye discs but not the expression of E2F target genes, suggesting that the coordinated transcription of E2F target genes does not significantly affect the pattern of cell proliferation.

scholarly journals Highly efficient generation of canker resistant sweet orange enabled by an improved CRISPR/Cas9 system

2021 ◽  
Author(s):  
Xiaoen Huang ◽  
Nian Wang
Keyword(s):  
Genome Editing ◽  
Gene Editing ◽  
Target Genes ◽  
High Efficiency ◽  
Sweet Orange ◽  
Susceptibility Gene ◽  
Transformation Rate ◽  
Biallelic Mutation ◽  
Important Species ◽  
Citrus Production

Sweet orange (Citrus sinensis) is the most economically important species for the citrus industry. However, it is susceptible to many diseases including citrus bacterial canker caused by Xanthomonas citri subsp. citri (Xcc) that triggers devastating effects on citrus production. Conventional breeding has not met the challenge to improve disease resistance of sweet orange due to the long juvenility and other limitations. CRISPR-mediated genome editing has shown promising potentials for genetic improvements of plants. Generation of biallelic/homozygous mutants remains difficult for sweet orange due to low transformation rate, existence of heterozygous alleles for target genes and low biallelic editing efficacy using the CRISPR technology. Here, we report improvements in the CRISPR/Cas9 system for citrus gene editing. Based on the improvements we made previously (dicot codon optimized Cas9, tRNA for multiplexing, a modified sgRNA scaffold with high efficiency, CsU6 to drive sgRNA expression), we further improved our CRISPR/Cas9 system by choosing superior promoters (CmYLCV or CsUbi promoter) to drive Cas9 and optimizing culture temperature. This system was able to generate a biallelic mutation rate of up to 89% for Carrizo citrange and 79% for Hamlin sweet orange. Consequently, this system was used to generate canker resistant Hamlin sweet orange by mutating the effector binding element (EBE) of canker susceptibility gene CsLOB1, which is required for causing canker symptoms by Xcc. Six biallelic Hamlin sweet orange mutant lines in the EBE were generated. The biallelic mutants are resistant to Xcc. Biallelic mutation of the EBE region abolishes the induction of CsLOB1 by Xcc. This study represents a significant improvement in sweet orange gene editing efficacy and generating disease resistant varieties via CRISPR-mediated genome editing. This improvement in citrus genome editing makes genetic studies and manipulations of sweet orange more feasible.

scholarly journals Elucidating the Mechanisms of Hugan Buzure Granule in the Treatment of Liver Fibrosis via Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yi Zhu ◽  
Ming Qiao ◽  
Jianhua Yang ◽  
Junping Hu
Keyword(s):  
Liver Fibrosis ◽  
Rna Polymerase Ii ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Docking Simulation ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Transcription Activator ◽  
Active Ingredients ◽  
Oxidoreductase Activity

Objective. To holistically explore the latent active ingredients, targets, and related mechanisms of Hugan buzure granule (HBG) in the treatment of liver fibrosis (LF) via network pharmacology. Methods. First, we collected the ingredients of HBG by referring the TCMSP server and literature and filtered the active ingredients though the criteria of oral bioavailability ≥30% and drug-likeness index ≥0.18. Second, herb-associated targets were predicted and screened based on the BATMAN-TCM and SwissTargetPrediction platforms. Candidate targets related to LF were collected from the GeneCards and OMIM databases. Furthermore, the overlapping target genes were used to construct the protein-protein interaction network and “drug-compound-target-disease” network. Third, GO and KEGG pathway analyses were carried out to illustrate the latent mechanisms of HBG in the treatment of LF. Finally, the combining activities of hub targets with active ingredients were further verified based on software AutoDock Vina. Results. A total of 25 active ingredients and 115 overlapping target genes of HBG and LF were collected. Besides, GO enrichment analysis exhibited that the overlapping target genes were involved in DNA-binding transcription activator activity, RNA polymerase II-specific, and oxidoreductase activity. Simultaneously, the key molecular mechanisms of HBG against LF were mainly involved in PI3K-AKT, MAPK, HIF-1, and NF-κB signaling pathways. Also, molecular docking simulation demonstrated that the key targets of HBG for antiliver fibrosis were IL6, CASP3, EGFR, VEGF, and MAPK. Conclusion. This work validated and predicted the underlying mechanisms of multicomponent and multitarget about HBG in treating LF and provided a scientific foundation for further research.

scholarly journals TargeTALE: A Web Resource to Identify TALEs in Xanthomonas Genomes and Their Respective Targets

2019 ◽  
Vol 32 (12) ◽  
pp. 1577-1580
Author(s):  
Frederico Schmitt Kremer ◽  
Amanda Munari Guimarães ◽  
Christian Domingues Sanchez ◽  
Luciano da Silva Pinto
Keyword(s):  
Target Genes ◽  
Economic Value ◽  
Gram Negative Bacteria ◽  
Expression Data ◽  
Proof Of Concept ◽  
Host Gene Expression ◽  
Transcription Activator ◽  
Gram Negative ◽  
Web Resource ◽  
Concept Validation

The Xanthomonas genus, comprises more than 30 species of gram-negative bacteria, most of which are pathogens of plants with high economic value, such as rice, common bean, and maize. Transcription activator-like effectors (TALEs), which act by regulating the host gene expression, are some of the major virulence factors of these bacteria. We present a novel tool to identify TALE genes in the genome of Xanthomonas strains and their respective targets. The analysis of the results obtained by TargeTALE in a proof-of-concept validation demonstrate that, at optimum setting, approximately 93% of the predicted target genes with available expression data were confirmed as upregulated during the infection, indicating that the tool might be useful for researchers in the field.

scholarly journals Identification of Sp1 as a Transcription Activator to Regulate Fibroblast Growth Factor 21 Gene Expression

2017 ◽  
Vol 2017 ◽  
pp. 1-10
Author(s):  
Shuqin Chen ◽  
Huating Li ◽  
Jing Zhang ◽  
Shan Jiang ◽  
Mingliang Zhang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Target Genes ◽  
Proximal Promoter ◽  
Fibroblast Growth Factor 21 ◽  
Obese Mouse ◽  
Primary Role ◽  
Fibroblast Growth ◽  
Transcription Activator

Fibroblast growth factor 21 (FGF21) is a metabolic hormone with multiple beneficial effects on lipid and glucose homeostasis. Previous study demonstrated that FGF21 might be one of the Sp1 target genes. However, the transcriptional role of Sp1 on FGF21 in adipose tissue and liver has not been reported. In this study, we found that the proximal promoter of mouse FGF21 is located between −63 and −20 containing two putative Sp1-binding sites. Sp1 is a mammalian transcription factor involved in the regulation of many genes during physiological and pathological processes. Our study showed that overexpression of Sp1 or suppressing Sp1 expression resulted in increased or reduced FGF21 promoter activity, respectively. Mutation analysis demonstrated that the Sp1-binding site located between −46 and −38 plays a primary role in transcription of FGF21. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis indicated that Sp1 specifically bound to this region. Furthermore, the binding activity of Sp1 was significantly increased in adipose tissues of HFD-induced obese mouse and liver of DEN-treated mouse. Thus, our results demonstrate that Sp1 positively regulates the basal transcription of FGF21 in the liver and adipose tissue and contributes to the obesity-induced FGF21 upregulation in mouse adipose tissue and hepatic FGF21 upregulation in hepatocarcinogenesis.

scholarly journals Maximal Induction of a Subset of Interferon Target Genes Requires the Chromatin-Remodeling Activity of the BAF Complex

2002 ◽  
Vol 22 (18) ◽  
pp. 6471-6479 ◽  
Author(s):  
Hong Liu ◽  
Hyeog Kang ◽  
Rui Liu ◽  
Xin Chen ◽  
Keji Zhao
Keyword(s):  
Chromatin Remodeling ◽  
Target Genes ◽  
Transcription Activator ◽  
Baf Complex ◽  
Antiproliferative Effects ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Maximal Induction ◽  
Antiproliferative Activities

ABSTRACT The mammalian SWI/SNF-like chromatin-remodeling BAF complex plays several important roles in controlling cell proliferation and differentiation. Interferons (IFNs) are key mediators of cellular antiviral and antiproliferative activities. In this report, we demonstrate that the BAF complex is required for the maximal induction of a subset of IFN target genes by alpha IFN (IFN-α). The BAF complex is constitutively associated with the IFITM3 promoter in vivo and facilitates the chromatin remodeling of the promoter upon IFN-α induction. Furthermore, we show that the ubiquitous transcription activator Sp1 interacts with the BAF complex in vivo and augments the BAF-mediated activation of the IFITM3 promoter. Sp1 binds constitutively to the IFITM3 promoter in the absence of the BAF complex, suggesting that it may recruit and/or stabilize the BAF complex binding to the IFITM3 promoter. Our results bring new mechanistic insights into the antiproliferative effects of the chromatin-remodeling BAF complex.

scholarly journals Suppression of PTEN Expression by NF-κB Prevents Apoptosis

2004 ◽  
Vol 24 (3) ◽  
pp. 1007-1021 ◽  
Author(s):  
Krishna Murthi Vasudevan ◽  
Sushma Gurumurthy ◽  
Vivek M. Rangnekar
Keyword(s):  
Dna Binding ◽  
Target Genes ◽  
Negative Regulator ◽  
Pten Expression ◽  
Pten Gene ◽  
Transcription Activator ◽  
Potent Inducer ◽  
Protein Levels ◽  
Induced Apoptosis ◽  
Regulatory Loop

ABSTRACT NF-κB is a heterodimeric transcription activator consisting of the DNA binding subunit p50 and the transactivation subunit p65/RelA. NF-κB prevents cell death caused by tumor necrosis factor (TNF) and other genotoxic insults by directly inducing antiapoptotic target genes. We report here that the tumor suppressor PTEN, which functions as a negative regulator of phosphatidylinositol (PI)-3 kinase/Akt-mediated cell survival pathway, is down regulated by p65 but not by p50. Moreover, a subset of human lung or thyroid cancer cells expressing high levels of endogenous p65 showed decreased expression of PTEN that could be rescued by specific inhibition of the NF-κB pathway with IκB overexpression as well as with small interfering RNA directed against p65. Importantly, TNF, a potent inducer of NF-κB activity, suppressed PTEN gene expression in IKKβ+/+ cells but not in IKKβ−/− cells, which are deficient in the NF-κB activation pathway. These findings indicated that NF-κB activation was necessary and sufficient for inhibition of PTEN expression. The promoter, RNA, and protein levels of PTEN are down-regulated by NF-κB. The mechanism underlying suppression of PTEN expression by NF-κB was independent of p65 DNA binding or transcription function and involved sequestration of limiting pools of transcriptional coactivators CBP/p300 by p65. Restoration of PTEN expression inhibited NF-κB transcriptional activity and augmented TNF-induced apoptosis, indicating a negative regulatory loop involving PTEN and NF-κB. PTEN is, thus, a novel target whose suppression is critical for antiapoptosis by NF-κB.

scholarly journals A role for IRF3-dependent RXRα repression in hepatotoxicity associated with viral infections

2006 ◽  
Vol 203 (12) ◽  
pp. 2589-2602 ◽  
Author(s):  
Edward K. Chow ◽  
Antonio Castrillo ◽  
Arash Shahangian ◽  
Liming Pei ◽  
Ryan M. O'Connell ◽  
...  
Keyword(s):  
Viral Infection ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Viral Infections ◽  
Type I ◽  
Reye's Syndrome ◽  
Downstream Target ◽  
Antiviral Responses ◽  
Host Metabolism

Viral infections and antiviral responses have been linked to several metabolic diseases, including Reye's syndrome, which is aspirin-induced hepatotoxicity in the context of a viral infection. We identify an interferon regulatory factor 3 (IRF3)–dependent but type I interferon–independent pathway that strongly inhibits the expression of retinoid X receptor α (RXRα) and suppresses the induction of its downstream target genes, including those involved in hepatic detoxification. Activation of IRF3 by viral infection in vivo greatly enhances bile acid– and aspirin-induced hepatotoxicity. Our results provide a critical link between the innate immune response and host metabolism, identifying IRF3-mediated down-regulation of RXRα as a molecular mechanism for pathogen-associated metabolic diseases.

scholarly journals Recapitulation and reversal of schizophrenia-related phenotypes in Setd1a-deficient mice

2019 ◽  
Author(s):  
Jun Mukai ◽  
Enrico Cannavò ◽  
Ziyi Sun ◽  
Gregg Crabtree ◽  
Anastasia Diamantopoulou ◽  
...  
Keyword(s):  
Working Memory ◽  
Target Genes ◽  
Susceptibility Gene ◽  
Orthologous Gene ◽  
Therapeutic Interventions ◽  
Transferase Activity ◽  
Loss Of Function ◽  
Axonal Branching ◽  
Synaptic Dynamics ◽  
Deficient Mice

SummarySETD1A, a histone methyltransferase, is a key schizophrenia susceptibility gene. Mutant mice carrying a heterozygous loss-of-function mutation of the orthologous gene exhibit alterations in axonal branching and cortical synaptic dynamics, accompanied by specific deficits in working memory that recapitulates SCZ-related alterations. We show that Setd1a targets mostly enhancers and reveal a striking overlap between Setd1a and Mef2 chromatin targets. Setd1a targets are highly expressed in pyramidal neurons and enriched for genes with postnatally-biased expression involved in synaptic structure and function. Notably, evolutionary conserved Setd1a binding sites and target genes are strongly associated with neuropsychiatric genetic risk burden. Reinstating Setd1a expression in adulthood rescues working memory deficits. We identify LSD1 as a major demethylase counteracting the effects of Setd1a methyl transferase activity and show that LSD1 antagonism in adult Setd1a-deficient mice results in a full rescue of the behavioral abnormalities and axonal branching deficits. Our findings advance our understanding of how SETD1A mutations predispose to SCZ and point to therapeutic interventions.

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