scholarly journals SWI/SNF complexes act through CBP-1 histone acetyltransferase to regulate acute functional tolerance to alcohol

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Laura D. Mathies ◽  
Jonathan H. Lindsay ◽  
Amal P. Handal ◽  
GinaMari G. Blackwell ◽  
Andrew G. Davies ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
Human Populations ◽  
Wild Type ◽  
C Elegans ◽  
Membrane Microdomain ◽  
Acute Responses ◽  
Alcohol Response ◽  
Functional Tolerance ◽  
Control Construct

Abstract Background SWI/SNF chromatin remodeling genes are required for normal acute responses to alcohol in C. elegans and are associated with alcohol use disorder in two human populations. In an effort to discover the downstream genes that are mediating this effect, we identified SWI/SNF-regulated genes in C. elegans. Results To identify SWI/SNF-regulated genes in adults, we compared mRNA expression in wild type and swsn-1(os22ts) worms under conditions that produce inactive swsn-1 in mature cells. To identify SWI/SNF-regulated genes in neurons, we compared gene expression in swsn-9(ok1354) null mutant worms that harbor a neuronal rescue or a control construct. RNA sequencing was performed to an average depth of 25 million reads per sample using 50-base, paired-end reads. We found that 6813 transcripts were significantly differentially expressed between swsn-1(os22ts) mutants and wild-type worms and 2412 transcripts were significantly differentially expressed between swsn-9(ok1354) mutants and swsn-9(ok1354) mutants with neuronal rescue. We examined the intersection between these two datasets and identified 603 genes that were differentially expressed in the same direction in both comparisons; we defined these as SWI/SNF-regulated genes in neurons and in adults. Among the differentially expressed genes was cbp-1, a C. elegans homolog of the mammalian CBP/p300 family of histone acetyltransferases. CBP has been implicated in the epigenetic regulation in response to alcohol in animal models and a polymorphism in the human CBP gene, CREBBP, has been associated with alcohol-related phenotypes. We found that cbp-1 is required for the development of acute functional tolerance to alcohol in C. elegans. Conclusions We identified 603 transcripts that were regulated by two different SWI/SNF complex subunits in adults and in neurons. The SWI/SNF-regulated genes were highly enriched for genes involved in membrane rafts, suggesting an important role for this membrane microdomain in the acute alcohol response. Among the differentially expressed genes was cbp-1; CBP-1 homologs have been implicated in alcohol responses across phyla and we found that C. elegans cbp-1 was required for the acute alcohol response in worms.

scholarly journals Identification and characterization of differentially expressed genes in Caenorhabditis elegans in response to pathogenic and nonpathogenic Stenotrophomonas maltophilia

2019 ◽  
Author(s):  
Leah J Radeke ◽  
Michael Herman
Keyword(s):  
Candidate Genes ◽  
Differentially Expressed Genes ◽  
Stenotrophomonas Maltophilia ◽  
Defense Mechanisms ◽  
Virulent Strain ◽  
Differentially Expressed ◽  
Transcriptional Responses ◽  
Transcriptomic Response ◽  
C Elegans ◽  
Realistic Interaction

Abstract Background: Stenotrophomonas maltophilia is an emerging nosocomial pathogen that causes infection in immunocompromised patients. S. maltophilia isolates are genetically diverse, contain diverse virulence factors, and are variably pathogenic within several host species. Members of the Stenotrophomonas genus are part of the native microbiome of C. elegans , being found in greater relative abundance within the worm than its environment, suggesting that these bacteria accumulate within C. elegans . Thus, study of the C. elegans-Stenotrophomonas interaction is of both medical and ecological significance. To identify host defense mechanisms, we analyzed the C. elegans transcriptomic response to S. maltophilia strains of varying pathogenicity: K279a, an avirulent clinical isolate, JCMS, a virulent strain isolated in association with soil nematodes near Manhattan, KS, and JV3, an even more virulent environmental isolate. Results: Overall, we found 145 genes that are commonly differentially expressed in response to pathogenic S. maltophilia strains, 89% of which are upregulated, with many even further upregulated in response to JV3 as compared to JCMS. There are many more JV3-specific differentially expressed genes (225, 11% upregulated) than JCMS-specific differentially expressed genes (14, 86% upregulated), suggesting JV3 has unique pathogenic mechanisms that could explain its increased virulence. We used connectivity within a gene network model to choose pathogen-specific and strain-specific differentially expressed candidate genes for functional analysis. Mutations in 13 of 22 candidate genes caused significant differences in C. elegans survival in response to at least one S. maltophilia strain, although not always the strain that induced differential expression, suggesting a dynamic response to varying levels of pathogenicity. Conclusions: Variation in observed pathogenicity and differences in host transcriptional responses to S. maltophilia strains reveal that strain-specific mechanisms play important roles in S. maltophilia pathogenesis. Furthermore, utilizing bacteria closely related to strains found in C. elegans natural environment provides a more realistic interaction for understanding host-pathogen response.

scholarly journals A red herring in zebrafish genetics: allele-specific gene expression can underlie altered transcript abundance in zebrafish mutants

2021 ◽  
Author(s):  
Richard J White ◽  
Eirinn Mackay ◽  
Stephen W Wilson ◽  
Elisabeth M Busch-Nentwich
Keyword(s):  
Differentially Expressed Genes ◽  
Differentially Expressed Gene ◽  
Transcript Abundance ◽  
Differentially Expressed ◽  
Model Organisms ◽  
Specific Gene ◽  
Wild Type ◽  
Specific Expression ◽  
Genomic Location ◽  
Allele Specific

In model organisms, RNA sequencing is frequently used to assess the effect of genetic mutations on cellular and developmental processes. Typically, animals heterozygous for a mutation are crossed to produce offspring with different genotypes. Resultant embryos are grouped by genotype to compare homozygous mutant embryos to heterozygous and wild-type siblings. Genes that are differentially expressed between the groups are assumed to reveal insights into the pathways affected by the mutation. Here we show that in zebrafish, differentially expressed genes are often overrepresented on the same chromosome as the mutation due to different levels of expression of alleles from different genetic backgrounds. Using an incross of haplotype-resolved wild-type fish, we found evidence of widespread allele-specific expression, which appears as differential expression when comparing embryos homozygous for a region of the genome to their siblings. When analysing mutant transcriptomes, this means that differentially expressed genes on the same chromosome as a mutation of interest may not be caused by that mutation. Typically, the genomic location of a differentially expressed gene is not considered when interpreting its importance with respect to the phenotype. This could lead to pathways being erroneously implicated or overlooked due to the noise of spurious differentially expressed genes on the same chromosome as the mutation. These observations have implications for the interpretation of RNA-seq experiments involving outbred animals and non-inbred model organisms.

Extracting Biological Significant Subnetworks from Protein-Protein Interactions Induced by Differentially Expressed Genes of HIV-1 Vpr Variants

2015 ◽  
Vol 4 (4) ◽  
pp. 35-51 ◽  
Author(s):  
Bandana Barman ◽  
Anirban Mukhopadhyay
Keyword(s):  
Differentially Expressed Genes ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Wild Type ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Hiv 1

Identification of protein interaction network is very important to find the cell signaling pathway for a particular disease. The authors have found the differentially expressed genes between two sample groups of HIV-1. Samples are wild type HIV-1 Vpr and HIV-1 mutant Vpr. They did statistical t-test and found false discovery rate (FDR) to identify the genes increased in expression (up-regulated) or decreased in expression (down-regulated). In the test, the authors have computed q-values of test to identify minimum FDR which occurs. As a result they found 172 differentially expressed genes between their sample wild type HIV-1 Vpr and HIV-1 mutant Vpr, R80A. They found 68 up-regulated genes and 104 down-regulated genes. From the 172 differentially expressed genes the authors found protein-protein interaction network with string-db and then clustered (subnetworks) the PPI networks with cytoscape3.0. Lastly, the authors studied significance of subnetworks with performing gene ontology and also studied the KEGG pathway of those subnetworks.

scholarly journals Differential Potential of Phytophthora capsici Resistance Mechanisms to the Fungicide Metalaxyl in Peppers

2020 ◽  
Vol 8 (2) ◽  
pp. 278 ◽  
Author(s):  
Weiyan Wang ◽  
Xiao Liu ◽  
Tao Han ◽  
Kunyuan Li ◽  
Yang Qu ◽  
...  
Keyword(s):  
Mutant Strain ◽  
Differentially Expressed Genes ◽  
Phytophthora Capsici ◽  
Resistance Mechanism ◽  
Resistant Mutant ◽  
Resistance Mechanisms ◽  
Differentially Expressed ◽  
Pathogenicity Test ◽  
Wild Type ◽  
Metalaxyl Resistance

Metalaxyl is one of the main fungicides used to control pepper blight caused by Phytophthora capsici. Metalaxyl resistance of P. capsici, caused by the long-term intense use of this fungicide, has become one of the most serious challenges facing pest management. To reveal the potential resistance mechanism of P. capsici to fungicide metalaxyl, a metalaxyl-resistant mutant strain SD1-9 was obtained under laboratory conditions. The pathogenicity test showed that mutant strain SD1-9 had different pathogenicity to different host plants with or without the treatment of metalaxyl compared with that of the wild type SD1. Comparative transcriptome sequencing of mutant strain SD1-9 and wild type SD1 led to the identification of 3845 differentially expressed genes, among them, 517 genes were upregulated, while 3328 genes were down-regulated in SD1-9 compared to that in the SD1. The expression levels of 10 genes were further verified by real-time RT-PCR. KEGG analysis showed that the differentially expressed genes were enriched in the peroxisome, endocytosis, alanine and tyrosine metabolism. The expression of the candidate gene XLOC_020226 during 10 life history stages was further studied, the results showed that expression level reached a maximum at the zoospores stage and basically showed a gradually increasing trend with increasing infection time in pepper leaves in SD1-9 strain, while its expression gradually increased in the SD1 strain throughout the 10 stages, indicated that XLOC_020226 may be related to the growth and pathogenicity of P. capsici. In summary, transcriptome analysis of plant pathogen P. capsici strains with different metalaxyl resistance not only provided database of the genes involved in the metalaxyl resistance of P. capsici, but also allowed us to gain novel insights into the potential resistance mechanism of P. capsici to metalaxyl in peppers.

scholarly journals Effect of Transgenesis on mRNA and miRNA Profiles in Cucumber Fruits Expressing Thaumatin II

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 334 ◽  
Author(s):  
Magdalena Ewa Pawełkowicz ◽  
Agnieszka Skarzyńska ◽  
Małgorzata Sroka ◽  
Maria Szwacka ◽  
Tomasz Pniewski ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
Transgenic Crop ◽  
Unintended Effects ◽  
Wild Type ◽  
Cucumis Sativus L ◽  
Breeding Programs ◽  
Minimal Impact ◽  
Gene Ontology Classification ◽  
Transgenic Lines

Transgenic plants are commonly used in breeding programs because of the various features that can be introduced. However, unintended effects caused by genetic transformation are still a topic of concern. This makes research on the nutritional safety of transgenic crop plants extremely interesting. Cucumber (Cucumis sativus L.) is a crop that is grown worldwide. The aim of this study was to identify and characterize differentially expressed genes and regulatory miRNAs in transgenic cucumber fruits that contain the thaumatin II gene, which encodes the sweet-tasting protein thaumatin II, by NGS sequencing. We compared the fruit transcriptomes and miRNomes of three transgenic cucumber lines with wild-type cucumber. In total, we found 47 differentially expressed genes between control and all three transgenic lines. We performed the bioinformatic functional analysis and gene ontology classification. We also identified 12 differentially regulated miRNAs, from which three can influence the two targets (assigned as DEGs) in one of the studied transgenic lines (line 224). We found that the transformation of cucumber with thaumatin II and expression of the transgene had minimal impact on gene expression and epigenetic regulation by miRNA, in the cucumber fruits.

scholarly journals Transcriptomic analysis of PPARα-dependent alterations during cardiac hypertrophy

2008 ◽  
Vol 36 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Pascal J. H. Smeets ◽  
Heleen M. de Vogel-van den Bosch ◽  
Peter H. M. Willemsen ◽  
Alphons P. Stassen ◽  
Torik Ayoubi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Lipid Metabolism ◽  
Cardiac Hypertrophy ◽  
Signaling Pathways ◽  
Differentially Expressed Genes ◽  
Left Ventricular ◽  
Transcriptomic Analysis ◽  
Differentially Expressed ◽  
Wild Type

Peroxisome proliferator-activated receptor (PPAR)α regulates lipid metabolism at the transcriptional level and modulates the expression of genes involved in inflammation, cell proliferation, and differentiation. Although PPARα has been shown to mitigate cardiac hypertrophy, knowledge about underlying mechanisms and the nature of signaling pathways involved is fragmentary and incomplete. The aim of this study was to identify the processes and signaling pathways regulated by PPARα in hearts challenged by a chronic pressure overload by means of whole genome transcriptomic analysis. PPARα−/− and wild-type mice were subjected to transverse aortic constriction (TAC) for 28 days, and left ventricular gene expression profile was determined with Affymetrix GeneChip Mouse Genome 430 2.0 arrays containing >45,000 probe sets. In unchallenged hearts, the mere lack of PPARα resulted in 821 differentially expressed genes, many of which are related to lipid metabolism and immune response. TAC resulted in a more pronounced cardiac hypertrophy and more extensive changes in gene expression (1,910 and 312 differentially expressed genes, respectively) in PPARα−/− mice than in wild-type mice. Many of the hypertrophy-related genes were related to development, signal transduction, actin filament organization, and collagen synthesis. Compared with wild-type hypertrophied hearts, PPARα−/− hypertrophied hearts revealed enrichment of gene clusters related to extracellular matrix remodeling, immune response, oxidative stress, and inflammatory signaling pathways. The present study therefore demonstrates that, in addition to lipid metabolism, PPARα is an important modulator of immune and inflammatory response in cardiac muscle.

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