scholarly journals CG methylation covaries with differential gene expression between leaf and floral bud tissues of Brachypodium distachyon

2015 ◽  
Author(s):  
Kyria Roessler ◽  
Shohei Takuno ◽  
Brandon Gaut
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Sequence Data ◽  
Brachypodium Distachyon ◽  
Grass Species ◽  
Specific Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Model Grass ◽  
Floral Bud

DNA methylation has the potential to influence plant growth and development through its influence on gene expression. To date, however, the evidence from plant systems is mixed as to whether patterns of DNA methylation vary significantly among tissues and, if so, whether these differences affect tissue-specific gene expression. To address these questions, we analyzed both bisulfite sequence (BSseq) and transcriptomic sequence data from three biological replicates of two tissues (leaf and floral bud) from the model grass species Brachypodium distachyon. Our first goal was to determine whether tissues were more differentiated in DNA methylation than explained by variation among biological replicates. Tissues were more differentiated than biological replicates, but the analysis of replicated data revealed high (>50%) false positive rates for the inference of differentially methylated sites (DMSs) and differentially methylated regions (DMRs). Comparing methylation to gene expression, we found that differential CG methylation consistently covaried negatively with gene expression, regardless as to whether methylation was within genes, within their promoters or even within their closest transposable element. The relationship between gene expression and either CHG or CHH methylation was less consistent. In total, CG methylation in promoters explained 9% of the variation in tissue-specific expression across genes, suggesting that CG methylation is a minor but appreciable factor in tissue differentiation.

scholarly journals Methylation of the Cyclin A1 Promoter Correlates with Gene Silencing in Somatic Cell Lines, while Tissue-Specific Expression of Cyclin A1 Is Methylation Independent

2000 ◽  
Vol 20 (9) ◽  
pp. 3316-3329 ◽  
Author(s):  
Carsten Müller ◽  
Carol Readhead ◽  
Sven Diederichs ◽  
Gregory Idos ◽  
Rong Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Promoter Methylation ◽  
Cpg Island ◽  
Trichostatin A ◽  
Specific Gene ◽  
Cyclin A1 ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression

ABSTRACT Gene expression in mammalian organisms is regulated at multiple levels, including DNA accessibility for transcription factors and chromatin structure. Methylation of CpG dinucleotides is thought to be involved in imprinting and in the pathogenesis of cancer. However, the relevance of methylation for directing tissue-specific gene expression is highly controversial. The cyclin A1 gene is expressed in very few tissues, with high levels restricted to spermatogenesis and leukemic blasts. Here, we show that methylation of the CpG island of the human cyclin A1 promoter was correlated with nonexpression in cell lines, and the methyl-CpG binding protein MeCP2 suppressed transcription from the methylated cyclin A1 promoter. Repression could be relieved by trichostatin A. Silencing of a cyclin A1 promoter-enhanced green fluorescent protein (EGFP) transgene in stable transfected MG63 osteosarcoma cells was also closely associated with de novo promoter methylation. Cyclin A1 could be strongly induced in nonexpressing cell lines by trichostatin A but not by 5-aza-cytidine. The cyclin A1 promoter-EGFP construct directed tissue-specific expression in male germ cells of transgenic mice. Expression in the testes of these mice was independent of promoter methylation, and even strong promoter methylation did not suppress promoter activity. MeCP2 expression was notably absent in EGFP-expressing cells. Transcription from the transgenic cyclin A1 promoter was repressed in most organs outside the testis, even when the promoter was not methylated. These data show the association of methylation with silencing of the cyclin A1 gene in cancer cell lines. However, appropriate tissue-specific repression of the cyclin A1 promoter occurs independently of CpG methylation.

scholarly journals Impact of Transposable Elements on Methylation and Gene Expression across Natural Accessions of Brachypodium distachyon

2020 ◽  
Vol 12 (11) ◽  
pp. 1994-2001 ◽  
Author(s):  
Michele Wyler ◽  
Christoph Stritt ◽  
Jean-Claude Walser ◽  
Célia Baroux ◽  
Anne C Roulin
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transposable Elements ◽  
Brachypodium Distachyon ◽  
Large Fraction ◽  
Expression Patterns ◽  
Specific Gene ◽  
Differential Gene ◽  
The Relationship ◽  
Silent State

Abstract Transposable elements (TEs) constitute a large fraction of plant genomes and are mostly present in a transcriptionally silent state through repressive epigenetic modifications, such as DNA methylation. TE silencing is believed to influence the regulation of adjacent genes, possibly as DNA methylation spreads away from the TE. Whether this is a general principle or a context-dependent phenomenon is still under debate, pressing for studying the relationship between TEs, DNA methylation, and nearby gene expression in additional plant species. Here, we used the grass Brachypodium distachyon as a model and produced DNA methylation and transcriptome profiles for 11 natural accessions. In contrast to what is observed in Arabidopsis thaliana, we found that TEs have a limited impact on methylation spreading and that only few TE families are associated with a low expression of their adjacent genes. Interestingly, we found that a subset of TE insertion polymorphisms is associated with differential gene expression across accessions. Thus, although not having a global impact on gene expression, distinct TE insertions may contribute to specific gene expression patterns in B. distachyon.

scholarly journals Starvation resistance and tissue-specific gene expression of stress-related genes in a naturally inbred ant population

2016 ◽  
Vol 3 (4) ◽  
pp. 160062 ◽  
Author(s):  
Nick Bos ◽  
Unni Pulliainen ◽  
Liselotte Sundström ◽  
Dalial Freitak
Keyword(s):  
Gene Expression ◽  
Stress Responses ◽  
Specific Gene ◽  
Starvation Resistance ◽  
Specific Expression ◽  
Tissue Specific ◽  
Trade Offs ◽  
Stress Related Genes ◽  
The Individual ◽  
Different Tissues

Starvation is one of the most common and severe stressors in nature. Not only does it lead to death if not alleviated, it also forces the starved individual to allocate resources only to the most essential processes. This creates energetic trade-offs which can lead to many secondary challenges for the individual. These energetic trade-offs could be exacerbated in inbred individuals, which have been suggested to have a less efficient metabolism. Here, we studied the effect of inbreeding on starvation resistance in a natural population of Formica exsecta ants, with a focus on survival and tissue-specific expression of stress, metabolism and immunity-related genes. Starvation led to large tissue-specific changes in gene expression, but inbreeding had little effect on most of the genes studied. Our results illustrate the importance of studying stress responses in different tissues instead of entire organisms.

scholarly journals A non-coding genetic variant maximally associated with serum urate levels is functionally linked to HNF4A-dependent PDZK1 expression

2018 ◽  
Author(s):  
Sarada Ketharnathan ◽  
Megan Leask ◽  
James Boocock ◽  
Amanda J. Phipps-Green ◽  
Jisha Antony ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Genetic Variant ◽  
Fluorescent Protein ◽  
Serum Urate ◽  
Specific Gene ◽  
Specific Expression ◽  
Enhancer Activity ◽  
Tissue Specific

ABSTRACTSeveral dozen genetic variants associate with serum urate levels, but the precise molecular mechanisms by which they affect serum urate are unknown. Here we tested for functional linkage of the maximally-associated genetic variant rs1967017 at the PDZK1 locus to elevated PDZK1 expression.We performed expression quantitative trait locus (eQTL) and likelihood analyses followed by gene expression assays. Zebrafish were used to determine the ability of rs1967017 to direct tissue-specific gene expression. Luciferase assays in HEK293 and HepG2 cells measured the effect of rs1967017 on transcription amplitude.PAINTOR analysis revealed rs1967017 as most likely to be causal and rs1967017 was an eQTL for PDZK1 in the intestine. The region harboring rs1967017 was capable of directly driving green fluorescent protein expression in the kidney, liver and intestine of zebrafish embryos, consistent with a conserved ability to confer tissue-specific expression. The urate-increasing T-allele of rs1967017 strengthens a binding site for the transcription factor HNF4A. siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. Luciferase assays showed that the T-allele of rs1967017 gains enhancer activity relative to the urate-decreasing C-allele, with T-allele enhancer activity abrogated by HNF4A depletion. HNF4A physically binds the rs1967017 region, suggesting direct transcriptional regulation of PDZK1 by HNF4A.With other reports our data predict that the urate-raising T-allele of rs1967017 enhances HNF4A binding to the PDZK1 promoter, thereby increasing PDZK1 expression. As PDZK1 is a scaffold protein for many ion channel transporters, increased expression can be predicted to increase activity of urate transporters and alter excretion of urate.

scholarly journals A Floxed exon (Flexon) approach to Cre-mediated conditional gene expression

2021 ◽  
Author(s):  
Justin M Shaffer ◽  
Iva Greenwald
Keyword(s):  
Gene Expression ◽  
Specific Protein ◽  
Specific Gene ◽  
Coding Region ◽  
Specific Expression ◽  
Control Of Gene Expression ◽  
Tissue Specific ◽  
Nonsense Mediated Decay ◽  
Conditional Gene Expression ◽  
Stop Cassette

Conditional gene expression allows for genes to be manipulated and lineages to be marked during development. In the established "lox-stop-lox" approach, Cre-mediated tissue-specific gene expression is achieved by excising the stop cassette, a lox-flanked translational stop that is inserted into the 5' untranslated region of a gene to halt its expression. Although lox-stop-lox has been successfully used in many experimental systems, the design of traditional stop cassettes also has common issues and limitations. Here, we describe the Floxed exon (Flexon), a stop cassette within an artificial exon that can be inserted flexibly into the coding region of any gene to cause premature termination of translation and nonsense-mediated decay of the mRNA. We demonstrate its efficacy in C. elegans by showing that, when promoters that cause weak and/or transient cell-specific expression are used to drive Cre in combination with a gfp(flexon) transgene, strong and sustained expression is obtained in specific lineages. We also describe several potential additional applications for using Flexon for developmental studies, including more precise control of gene expression using intersectional methods, tissue-specific protein degradation or RNAi, and generation of genetic mosaics. The Flexon approach should be feasible in any system where any site-specific recombination-based method may be applied.

scholarly journals Predicting tissue-specific gene expression from whole blood transcriptome

2020 ◽  
Author(s):  
Mahashweta Basu ◽  
Kun Wang ◽  
Eytan Ruppin ◽  
Sridhar Hannenhalli
Keyword(s):  
Gene Expression ◽  
Whole Blood ◽  
Specific Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Complex Disorders ◽  
Tissue Specific Gene ◽  
Tissue Specific Expression ◽  
Specific Gene Expression ◽  
Blood Transcriptome

AbstractComplex diseases are systemic, largely mediated via transcriptional dysregulation in multiple tissues. Thus, knowledge of tissue-specific transcriptome in an individual can provide important information about an individual’s health. Unfortunately, with a few exceptions such as blood, skin, and muscle, an individual’s tissue-specific transcriptome is not accessible through non-invasive means. However, due to shared genetics and regulatory programs between tissues, the transcriptome in blood may be predictive of those in other tissues, at least to some extent. Here, based on GTEx data, we address this question in a rigorous, systematic manner, for the first time. We find that an individual’s whole blood gene expression and splicing profile can predict tissue-specific expression levels in a significant manner (beyond demographic variables) for many genes. On average, across 32 tissues, the expression of about 60% of the genes is predictable from blood expression in a significant manner, with a maximum of 81% of the genes for the musculoskeletal tissue. Remarkably, the tissue-specific expression inferred from the blood transcriptome is almost as good as the actual measured tissue expression in predicting disease state for six different complex disorders, including Hypertension and Type 2 diabetes, substantially surpassing predictors built directly from the blood transcriptome. The code for our pipeline for tissue-specific gene expression prediction – TEEBoT, is provided, enabling others to study its potential translational value in other indications.

scholarly journals Impact of transposable elements on methylation and gene expression across natural accessions of Brachypodium distachyon

2020 ◽  
Author(s):  
Michele Wyler ◽  
Christoph Stritt ◽  
Jean-Claude Walser ◽  
Célia Baroux ◽  
Anne C. Roulin
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transposable Elements ◽  
Plant Species ◽  
Brachypodium Distachyon ◽  
Expression Patterns ◽  
Small Subset ◽  
Molecular Evidence ◽  
Specific Gene ◽  
Plant Genomes

AbstractTransposable elements (TEs) constitute a large fraction of plant genomes and are mostly present in a transcriptionally silent state through repressive epigenetic modifications such as DNA methylation. TE silencing is believed to influence the regulation of adjacent genes, possibly as DNA methylation spreads away from the TE. Whether this is a general principle or a context-dependent phenomenon is still under debate, pressing for studying the relationship between TEs, DNA methylation and nearby gene expression in additional plant species. Here we used the grass Brachypodium distachyon as a model and produced DNA methylation and transcriptome profiles for eleven natural accessions. In contrast to what is observed in Arabidopsis thaliana, we found that TEs have a limited impact on methylation spreading and that only few TE families are associated to a low expression of their adjacent genes. Interestingly, we found that a subset of TE insertion polymorphisms is associated with differential gene expression across accessions. Thus, although not having a global impact on gene expression, distinct TE insertions may contribute to specific gene expression patterns in B. distachyon.Significance statementTransposable elements (TEs) are a major component of plant genomes and a source of genetic and epigenetic innovations underlying adaptation to changing environmental conditions. Yet molecular evidence linking TE silencing and nearby gene expression are lacking for many plant species. We show that in the model grass Brachypodium DNA methylation spreads over very short distances around TEs, with an influence on gene expression for a small subset of TE families.

scholarly journals Sex-specific expression and DNA methylation in a species with extreme sexual dimorphism and paternal genome elimination

2020 ◽  
Author(s):  
Stevie A. Bain ◽  
Hollie Marshall ◽  
Laura Ross
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Alternative Splicing ◽  
Sexual Dimorphism ◽  
Planococcus Citri ◽  
Specific Gene ◽  
Paternal Genome ◽  
Specific Expression ◽  
Cis Acting ◽  
Genome Wide

AbstractSexual dimorphism is exhibited in many species across the tree of life with many phenotypic differences mediated by differential expression and alternative splicing of genes present in both sexes. However, the mechanisms that regulate these sex-specific expression and splicing patterns remain poorly understood. The mealybug, Planococcus citri, displays extreme sexual dimorphism and exhibits an unusual instance of sex-specific genomic imprinting, Paternal Genome Elimination (PGE), in which the paternal chromosomes in males are highly condensed and eliminated from the sperm. P. citri also has no sex chromosomes and as such both sexual dimorphism and PGE are predicted to be under epigenetic control. We recently showed that P. citri females display a highly unusual DNA methylation profile for an insect species, with the presence of promoter methylation associated with lower levels of gene expression. In this study we therefore decided to explore genome-wide differences in DNA methylation between male and female P. citri using whole genome bisulfite sequencing. We have identified extreme differences in genome-wide levels and patterns between the sexes. Males display overall higher levels of DNA methylation which manifests as more uniform low-levels across the genome. Whereas females display more targeted high levels of methylation. We suggest these unique sex-specific differences are due to chromosomal differences caused by PGE and may be linked to possible ploidy compensation. Using RNA-Seq we identified extensive sex-specific gene expression and alternative splicing. We found cis-acting DNA methylation is not directly associated with differentially expressed or differentially spliced genes, indicating a broader role for chromosome-wide trans-acting DNA methylation in this species.

scholarly journals Gene-Specific Methylation Profiles for Integrative Methylation-Expression Analysis in Cancer Research

2019 ◽  
Author(s):  
Yusha Liu ◽  
Keith A. Baggerly ◽  
Elias Orouji ◽  
Ganiraju Manyam ◽  
Huiqin Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Penalized Regression ◽  
Tissue Type ◽  
Specific Gene ◽  
Integrative Genomics ◽  
Tissue Specific ◽  
Cancer Subtypes ◽  
Shiny App ◽  
Gene Level

AbstractDNA methylation is a key epigenetic factor regulating gene expression. While promoter-associated methylation has been extensively studied, recent publications have revealed that functionally important methylation also occurs in intergenic and distal regions, and varies across genes and tissue types. Given the growing importance of inter-platform integrative genomic analyses, there is an urgent need to develop methods to construct gene-level methylation summaries that account for the potentially complex relationships between methylation and expression. We introduce a novel sequential penalized regression approach to construct gene-specific methylation profiles (GSMPs) which find for each gene and tissue type a sparse set of CpGs best explaining gene expression and weights indicating direction and strength of association. Using TCGA and MD Anderson colorectal cohorts to build and validate our models, we demonstrate our strategy better explains expression variability than standard approaches and produces gene-level scores showing key methylation differences across recently discovered colorectal cancer subtypes. We share an R Shiny app that presents GSMP results for colorectal, breast, and pancreatic cancer with plans to extend it to all TCGA cancer types. Our approach yields tissue-specific, gene-specific sparse lists of functionally important CpGs that can be used to construct gene-level methylation scores that are maximally correlated with gene expression for use in integrative models, and produce a tissue-specific summary of which genes appear to be strongly regulated by methylation. Our results introduce an important resource to the biomedical community for integrative genomics analyses involving DNA methylation.

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