scholarly journals N4-acetyldeoxycytosine DNA modification marks euchromatin regions in Arabidopsis thaliana

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Shuai Wang ◽  
Hairong Xie ◽  
Fei Mao ◽  
Haiyan Wang ◽  
Shu Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genomic Dna ◽  
Gene Expression Regulation ◽  
Detection Methods ◽  
Dna Modification ◽  
Protein Coding ◽  
Transcription Start Sites ◽  
Genome Wide ◽  
Multiple Detection ◽  
Cellular Dna

Abstract Background Direct analogs of chemically modified bases that carry important epigenetic information, such as 5-methylcytosine (m5C)/5-methyldeoxycytosine (5mC), 5-hydroxymethylcytosine (hm5C)/5-hydroxymethyldeoxycytosine (5hmC), and N6-methyladenosine (m6A)/N6-methyldeoxyadenosine (6mA), are detected in both RNA and DNA, respectively. The modified base N4-acetylcytosine (ac4C) is well studied in RNAs, but its presence and epigenetic roles in cellular DNA have not been explored. Results Here, we demonstrate the existence of N4-acetyldeoxycytosine (4acC) in genomic DNA of Arabidopsis with multiple detection methods. Genome-wide profiling of 4acC modification reveals that 4acC peaks are mostly distributed in euchromatin regions and present in nearly half of the expressed protein-coding genes in Arabidopsis. 4acC is mainly located around transcription start sites and positively correlates with gene expression levels. Imbalance of 5mC does not directly affect 4acC modification. We also characterize the associations of 4acC with 5mC and histone modifications that cooperatively regulate gene expression. Moreover, 4acC is also detected in genomic DNA of rice, maize, mouse, and human by mass spectrometry. Conclusions Our findings reveal 4acC as a hitherto unknown DNA modification in higher eukaryotes. We identify potential interactions of this mark with other epigenetic marks in gene expression regulation.

scholarly journals The open targets post-GWAS analysis pipeline

2020 ◽  
Vol 36 (9) ◽  
pp. 2936-2937 ◽  
Author(s):  
Gareth Peat ◽  
William Jones ◽  
Michael Nuhn ◽  
José Carlos Marugán ◽  
William Newell ◽  
...  
Keyword(s):  
Drug Targets ◽  
Gene Expression Regulation ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Protein Coding ◽  
Data Resource ◽  
Coding Regions ◽  
Genome Wide ◽  
Causal Genes ◽  
Interactive Data

Abstract Motivation Genome-wide association studies (GWAS) are a powerful method to detect even weak associations between variants and phenotypes; however, many of the identified associated variants are in non-coding regions, and presumably influence gene expression regulation. Identifying potential drug targets, i.e. causal protein-coding genes, therefore, requires crossing the genetics results with functional data. Results We present a novel data integration pipeline that analyses GWAS results in the light of experimental epigenetic and cis-regulatory datasets, such as ChIP-Seq, Promoter-Capture Hi-C or eQTL, and presents them in a single report, which can be used for inferring likely causal genes. This pipeline was then fed into an interactive data resource. Availability and implementation The analysis code is available at www.github.com/Ensembl/postgap and the interactive data browser at postgwas.opentargets.io.

scholarly journals Tri-methylation of Histone H3 Lysine 4 Facilitates Gene Expression in Ageing Cells

2017 ◽  
Author(s):  
Cristina Cruz ◽  
Monica Della Rosa ◽  
Christel Krueger ◽  
Qian Gao ◽  
Lucy Field ◽  
...  
Keyword(s):  
Gene Expression ◽  
Budding Yeast ◽  
Histone H3 ◽  
Specific Factor ◽  
Protein Coding ◽  
Replicative Lifespan ◽  
Protein Coding Genes ◽  
Genome Wide ◽  
Normal Expression ◽  
Transcriptional Induction

AbstractTranscription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which deposits di- and tri-methylation on histone H3 lysine 4 (H3K4) to form H3K4me2 and H3K4me3. Here we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeast. We find that COMPASS mutations dramatically reduce replicative lifespan and cause widespread gene expression defects. Known repressive functions of H3K4me2 are progressively lost with age, while hundreds of genes become dependent on H3K4me3 for full expression. Induction of these H3K4me3 dependent genes is also impacted in young cells lacking COMPASS components including the H3K4me3-specific factor Spp1. Remarkably, the genome-wide occurrence of H3K4me3 is progressively reduced with age despite widespread transcriptional induction, minimising the normal positive correlation between promoter H3K4me3 and gene expression. Our results provide clear evidence that H3K4me3 is required to attain normal expression levels of many genes across organismal lifespan.

scholarly journals Differential evolution in 3′UTRs leads to specific gene expression in Staphylococcus

2020 ◽  
Vol 48 (5) ◽  
pp. 2544-2563 ◽  
Author(s):  
Pilar Menendez-Gil ◽  
Carlos J Caballero ◽  
Arancha Catalan-Moreno ◽  
Naiara Irurzun ◽  
Inigo Barrio-Hernandez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Bacterial Species ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Species Differentiation ◽  
Orthologous Genes ◽  
Genome Wide ◽  
Sequence Variations ◽  
Species Specific

Abstract The evolution of gene expression regulation has contributed to species differentiation. The 3′ untranslated regions (3′UTRs) of mRNAs include regulatory elements that modulate gene expression; however, our knowledge of their implications in the divergence of bacterial species is currently limited. In this study, we performed genome-wide comparative analyses of mRNAs encoding orthologous proteins from the genus Staphylococcus and found that mRNA conservation was lost mostly downstream of the coding sequence (CDS), indicating the presence of high sequence diversity in the 3′UTRs of orthologous genes. Transcriptomic mapping of different staphylococcal species confirmed that 3′UTRs were also variable in length. We constructed chimeric mRNAs carrying the 3′UTR of orthologous genes and demonstrated that 3′UTR sequence variations affect protein production. This suggested that species-specific functional 3′UTRs might be specifically selected during evolution. 3′UTR variations may occur through different processes, including gene rearrangements, local nucleotide changes, and the transposition of insertion sequences. By extending the conservation analyses to specific 3′UTRs, as well as the entire set of Escherichia coli and Bacillus subtilis mRNAs, we showed that 3′UTR variability is widespread in bacteria. In summary, our work unveils an evolutionary bias within 3′UTRs that results in species-specific non-coding sequences that may contribute to bacterial diversity.

The COP9 signalosome influences the epigenetic landscape of Arabidopsis thaliana

2018 ◽  
Vol 35 (16) ◽  
pp. 2718-2723 ◽  
Author(s):  
Tamir Tuller ◽  
Alon Diament ◽  
Avital Yahalom ◽  
Assaf Zemach ◽  
Shimshi Atar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Arabidopsis Thaliana ◽  
Gene Expression Regulation ◽  
Developmental Pathways ◽  
Cop9 Signalosome ◽  
Supplementary Information ◽  
Loss Of Function ◽  
Genome Wide ◽  
High Level

Abstract Motivation The COP9 signalosome is a highly conserved multi-protein complex consisting of eight subunits, which influences key developmental pathways through its regulation of protein stability and transcription. In Arabidopsis thaliana, mutations in the COP9 signalosome exhibit a number of diverse pleiotropic phenotypes. Total or partial loss of COP9 signalosome function in Arabidopsis leads to misregulation of a number of genes involved in DNA methylation, suggesting that part of the pleiotropic phenotype is due to global effects on DNA methylation. Results We determined and analyzed the methylomes and transcriptomes of both partial- and total-loss-of-function Arabidopsis mutants of the COP9 signalosome. Our results support the hypothesis that the COP9 signalosome has a global genome-wide effect on methylation and that this effect is at least partially encoded in the DNA. Our analyses suggest that COP9 signalosome-dependent methylation is related to gene expression regulation in various ways. Differentially methylated regions tend to be closer in the 3D conformation of the genome to differentially expressed genes. These results suggest that the COP9 signalosome has a more comprehensive effect on gene expression than thought before, and this is partially related to regulation of methylation. The high level of COP9 signalosome conservation among eukaryotes may also suggest that COP9 signalosome regulates methylation not only in plants but also in other eukaryotes, including humans. Supplementary information Supplementary data are available at Bioinformatics online.

Nutrient Control of mRNA Translation

2020 ◽  
Vol 40 (1) ◽  
pp. 51-75 ◽  
Author(s):  
Xin Erica Shu ◽  
Robert V. Swanda ◽  
Shu-Bing Qian
Keyword(s):  
Gene Expression ◽  
Translational Control ◽  
Translational Regulation ◽  
Mrna Translation ◽  
Nutrient Sensing ◽  
Control Networks ◽  
Genome Wide ◽  
Nutrient Signaling ◽  
Specific Proteins ◽  
Cellular Dna

The emergence of genome-wide analyses to interrogate cellular DNA, RNA, and protein content has revolutionized the study of control networks that mediate cellular homeostasis. mRNA translation represents the last step of genetic flow and primarily defines the proteome. Translational regulation is thus critical for gene expression, in particular under nutrient excess or deficiency. Until recently, it was unclear how the global effects of translational control are orchestrated by nutrient signaling pathways. An emerging concept of translational reprogramming addresses how to maintain the expression of specific proteins during nutrient stress by translation of selective mRNAs. In this review, we describe recent advances in our understanding of translational control principles; nutrient-sensing mechanisms; and their dysregulation in human diseases such as diabetes, cancer, and aging. The mechanistic understanding of translational regulation in response to different nutrient conditions may help identify potential dietary and therapeutic targets to improve human health.

scholarly journals Pathogen Genetic Control of Transcriptome Variation in the Arabidopsis thaliana – Botrytis cinerea Pathosystem

Genetics ◽  
2020 ◽  
Vol 215 (1) ◽  
pp. 253-266 ◽  
Author(s):  
Nicole E. Soltis ◽  
Celine Caseys ◽  
Wei Zhang ◽  
Jason A. Corwin ◽  
Susanna Atwell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arabidopsis Thaliana ◽  
Botrytis Cinerea ◽  
Gene Expression Regulation ◽  
Expression Regulation ◽  
Necrotrophic Pathogen ◽  
Control Of Gene Expression ◽  
Genome Wide ◽  
Pathogen Control ◽  
Transcriptome Variation

In plant–pathogen relations, disease symptoms arise from the interaction of the host and pathogen genomes. Host–pathogen functional gene interactions are well described, whereas little is known about how the pathogen genetic variation modulates both organisms’ transcriptomes. To model and generate hypotheses on a generalist pathogen control of gene expression regulation, we used the Arabidopsis thaliana–Botrytis cinerea pathosystem and the genetic diversity of a collection of 96 B. cinerea isolates. We performed expression-based genome-wide association (eGWA) for each of 23,947 measurable transcripts in Arabidopsis (host), and 9267 measurable transcripts in B. cinerea (pathogen). Unlike other eGWA studies, we detected a relative absence of locally acting expression quantitative trait loci (cis-eQTL), partly caused by structural variants and allelic heterogeneity hindering their identification. This study identified several distantly acting trans-eQTL linked to eQTL hotspots dispersed across Botrytis genome that altered only Botrytis transcripts, only Arabidopsis transcripts, or transcripts from both species. Gene membership in the trans-eQTL hotspots suggests links between gene expression regulation and both known and novel virulence mechanisms in this pathosystem. Genes annotated to these hotspots provide potential targets for blocking manipulation of the host response by this ubiquitous generalist necrotrophic pathogen.

Detailed Genome-Wide DNA-Mapping of CD34+ Cells Purified from Patients with MDS Using High-Resolution SNP Arrays Identifies Significant Regions of Genomic Alterations.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2635-2635
Author(s):  
Daniel Nowak ◽  
Florian Wagner ◽  
Claudia C. Baldus ◽  
Olaf Hopfer ◽  
Maximilian Mossner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Copy Number ◽  
Genomic Dna ◽  
Genomic Mapping ◽  
Expression Data ◽  
Healthy Individuals ◽  
Window Width ◽  
Genome Wide ◽  
Cd34 Cells

Abstract Identification of common genomic lesions in progenitor cells of MDS Patients could lead to the discovery of new target genes in this disease and may be of prognostic value. Therefore, we carried out a detailed genome-wide mapping of genomic DNA from highly purified CD34+ progenitor cells from MDS patients and healthy individuals with high-resolution single nucleotide polymorphism (SNP) microarrays which scan 500,000 SNPs with a median inter-SNP distance of approximately 2.5 kb. Bone marrow aspirates were obtained from 14 MDS patients (IPSS low risk n=6, high risk n=8) and 6 healthy individuals after informed consent. CD34+ cells were purified by high gradient magnetic cell separation. Genomic DNA and RNA were extracted with standard TRIZOL technique and quality controlled with the Agilent Bioanalyzer 2100 and Nanodrop ND-1000 systems. 500 ng of each of the genomic DNA were processed according to the protocol of the Affymetrix 500 k NspI and StyI genomic mapping protocol, hybridized to 500 k NspI/StyI chip sets and scanned on an Affymetrix GeneChip scanner 3000. The median SNP call rate of analysed samples was 88.6% and ranged from 76.3% to 95.4%. One sample from the MDS patients and two samples from the healthy donors were excluded from analysis due to insufficient call rates. Raw signal intensity data was generated by the GCOS 4.0 software and imported into Partek Genomics 6.2 software. The control samples of healthy individuals were assigned a copy number of two and used as a reference baseline to calculate copy numbers in MDS samples. On the calculated values genomic smoothing was performed with a window width of 0.5 Mbps and a Gaussian width at half maximum 50% of window width. Significant regions of copy number alterations were calculated with a test region width of 0.5 Mbp and contiguous regions set to contain at least 1 Mbp (p<0.01). In addition, gene expression profiling (HG-U133 plus 2.0) was performed by standard Affymetrix technique. Numerous so far unknown significant regions of putative deletion or amplification which are not detectable by standard genomic analysis were discovered in MDS samples. Commonly deleted or amplificated regions appeared on chromosomes 1, 2, 3, 4, 5, 6, 11, 17, 19, 21 and 22. Gene lists of significant regions were created and subsequently used to perform a supervised analysis of gene expression data generated from the same bone marrow samples. This integration of genomic copy number analysis with global gene expression data showed that alterations of copy number directly affects gene expression patterns. In conclusion, this is the first high-density genomic mapping of CD34+ bone marrow cells from patients with MDS which could identify a number of so far unknown DNA-deletions/amplifications. These data contribute substantially to the understanding of the pathophysiology of MDS in greater detail and furthermore can be used to identify genes/regions which could resemble targets of new specific treatment options.

scholarly journals Gene Expression in Trypanosomatid Parasites

2010 ◽  
Vol 2010 ◽  
pp. 1-15 ◽  
Author(s):  
Santiago Martínez-Calvillo ◽  
Juan C. Vizuet-de-Rueda ◽  
Luis E. Florencio-Martínez ◽  
Rebeca G. Manning-Cela ◽  
Elisa E. Figueroa-Angulo
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Histone Variants ◽  
Protein Coding ◽  
Functional Studies ◽  
Polycistronic Transcription ◽  
General Transcription Factors ◽  
Genome Wide ◽  
Trypanosomatid Parasites

The parasitesLeishmaniaspp.,Trypanosoma brucei,andTrypanosoma cruziare the trypanosomatid protozoa that cause the deadly human diseases leishmaniasis, African sleeping sickness, and Chagas disease, respectively. These organisms possess unique mechanisms for gene expression such as constitutive polycistronic transcription of protein-coding genes and trans-splicing. Little is known about either the DNA sequences or the proteins that are involved in the initiation and termination of transcription in trypanosomatids.In silicoanalyses of the genome databases of these parasites led to the identification of a small number of proteins involved in gene expression. However, functional studies have revealed that trypanosomatids have more general transcription factors than originally estimated. Many posttranslational histone modifications, histone variants, and chromatin modifying enzymes have been identified in trypanosomatids, and recent genome-wide studies showed that epigenetic regulation might play a very important role in gene expression in this group of parasites. Here, we review and comment on the most recent findings related to transcription initiation and termination in trypanosomatid protozoa.

scholarly journals Gene-based association analysis identified 190 genes with polymorphisms affecting neuroticism

2020 ◽  
Author(s):  
Nadezhda M. Belonogova ◽  
Irina V. Zorkoltseva ◽  
Yakov A. Tsepilov ◽  
Tatiana I. Axenovich
Keyword(s):  
Gene Expression ◽  
Detailed Analysis ◽  
Association Analysis ◽  
Genetic Variants ◽  
Bioinformatics Analysis ◽  
Summary Statistics ◽  
Uk Biobank ◽  
Protein Coding ◽  
Pathogenic Variants ◽  
Genome Wide

AbstractRecent genome-wide studies have reported about 600 genes potentially influencing neuroticism. Little is known about the mechanisms of their action. Here, we aimed to conduct a more detailed analysis of genes whose polymorphisms can regulate the level of neuroticism. Using UK Biobank-based GWAS summary statistics, we performed a gene-based association analysis using four sets of genetic variants within a gene differing in their protein coding properties. To guard against the influence of strong GWAS signals outside the gene, we used the specially designed procedure. As a result, we identified 190 genes associated with neuroticism due to their polymorphisms. Thirty eight of these genes were novel. Within all genes identified, we distinguished two slightly overlapping groups comprising genes that demonstrated association when using protein-coding and non-coding SNPs. Many genes from the first group included potentially pathogenic variants. For some genes from the second group, we found evidence of pleiotropy with gene expression. We demonstrated that the association of almost two hundred known genes could be inflated by the GWAS signals outside the gene. Using bioinformatics analysis, we prioritized the neuroticism genes and showed that the genes influencing the trait by their polymorphisms are the most appropriate candidate genes.

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