Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA293240 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2173810_1.fastq.gz | Fastqsanger.gz | |||
| SRR2173810_2.fastq.gz | Fastqsanger.gz | |||
| SRR2173820_1.fastq.gz | Fastqsanger.gz | |||
| SRR2173820_2.fastq.gz | Fastqsanger.gz | |||
| SRR2173830_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Genetic loci displaying environmentally responsive epigenetic marks, termed metastable epialleles, offer a solution to the paradox presented by genetically identical yet phenotypically distinct individuals. The murine viable yellow agouti (Avy) locus is a well-described metastable epiallele that serves as a visual epigenetic biosensor. The Avy locus exhibits a high R-value or ratio of inter-individual (Vi) to inter-tissue (Vt) variance in gene expression, characteristic of what we term the ‘Agouti Expression Fingerprint.’ We propose a novel method for identification of candidate metastable epialleles based on the Agouti Expression Fingerprint, defining candidates as loci with R-values greater than 1.5 on expression microarray. Using Expression data from tissues of the three germ layers (liver, kidney, brain), high variance in agouti RNA levels among isogenic animals coupled with low variance among tissue types in individual animals is demonstrated. Here, we provide proof of concept for the ‘Agouti Expression Fingerprint’; the characterization of epigenetically labile loci in humans will be crucial to the development of novel screening and therapeutic targets for human disease prevention. For expression microarray studies, total RNA was isolated from liver, kidney, and brain tissue from 10 male Avy/a mice (2 per each of the 5 coat color classes) at time of weaning and coat color determination (day 22). Using Affymetrix GeneChip Mouse Genome 2.0 arrays (Santa Clara, CA), we queried the entire mouse genome for candidate metastable epialleles that display the Agouti Fingerprint. Approximately 100 of the greater than 40,000 transcripts on the mouse array displayed an expression pattern characterized as high inter-individual variation coupled with low inter-tissue variation (R-value > 1.5).
2011-07-14 | E-GEOD-28559 | biostudies-arrayexpress
Project description:Genetic loci displaying environmentally responsive epigenetic marks, termed metastable epialleles, offer a solution to the paradox presented by genetically identical yet phenotypically distinct individuals. The murine viable yellow agouti (Avy) locus is a well-described metastable epiallele that serves as a visual epigenetic biosensor. The Avy locus exhibits a high R-value or ratio of inter-individual (Vi) to inter-tissue (Vt) variance in gene expression, characteristic of what we term the ‘Agouti Expression Fingerprint.’ We propose a novel method for identification of candidate metastable epialleles based on the Agouti Expression Fingerprint, defining candidates as loci with R-values greater than 1.5 on expression microarray. Using Expression data from tissues of the three germ layers (liver, kidney, brain), high variance in agouti RNA levels among isogenic animals coupled with low variance among tissue types in individual animals is demonstrated. Here, we provide proof of concept for the ‘Agouti Expression Fingerprint’; the characterization of epigenetically labile loci in humans will be crucial to the development of novel screening and therapeutic targets for human disease prevention.
2011-07-15 | GSE28559 | GEO
Project description:An expression microarray approach for the identification of candidate metastable epialleles in the mouse genome
| PRJNA139039 | ENA
Project description:Genomic DNA was extracted from the livers of 5 22week old male mice, bisulfite converted and sequenced to ~30x coverage. The mice were obtained from two litters from an inbred agouti viable yellow colony. The individuals were isogenic but differed in their coat phenotype with one having a yellow coat, one a psuedoagouti coat and the remaining were phenotypically C57/BL6. The resulting DNA metylation profiles were investigated for individual differences in DNA methylation, including the identificaiton of novel metastable epialleles.
2015-12-01 | GSE72177 | GEO
Project description:Epialleles are meiotically inherited variations in expression states that are not linked to changes in DNA sequence. Although they are well documented to persist in plant genomes, their molecular origins are unknown. Here, we show using a variety of mutant and experimental populations that epialleles in Arabidopsis thaliana result from feedback regulation of pathways that primarily function to maintain DNA methylation at heterochromatin. Perturbations to maintenance of heterochromatin methylation leads to feedback regulation of DNA methylation in genes, with a preference for genes with pre-existing DNA methylation. Using epigenetic recombinant inbred lines (epiRIL), we show that epiallelic variation is enriched in euchromatin, yet, associated with QTL primarily located in heterochromatin. Mapping three-dimensional chromatin contacts reveals that genes that are hotspots for epiallelic variation have increased contact frequencies with regions possessing H3K9me2. Altogether, these data show that feedback regulation of pathways that evolved to maintain heterochromatin silencing leads to the origins of spontaneous epialleles.
2021-11-01 | GSE171157 | GEO
Project description:It is well established that epigenetic features, such as histone modifications and DNA methylation, are associated with gene expression across cell types. However, it is not well known how variation in genotype affects epigenetic state, or to what extent such variation contributes to variation in gene expression across genetically distinct individuals. Here we investigated the relationship between heritable epigenetic variation and gene expression in hepatocytes across nine inbred mouse strains. Eight of the inbred strains were founders of the diversity outbred (DO) mice, and the ninth was DBA/2J, which, along with C57BL/6J, is one of the founders of the BxD recombinant inbred panel of mice. We surveyed four histone modifications, H3K4me1, H3K4me3, H3K27me3 and H3K27ac, as well as DNA methylation. We used ChromHMM to identify 14 chromatin states representing distinct combinations of the four measured histone modifications. We found that variation in chromatin state mirrored genetic variation across the inbred strains. Furthermore, epigenetic variation was correlated with gene expression across strains. The correspondence between epigenetic state and gene expression was replicated in an independent population of DO mice in which we imputed local epigenetic state. In contrast, we found that DNA methylation did not vary across inbred strains and was not correlated with variation in expression in DO mice. This work suggests that chromatin state is highly influenced by local genotype and may be a primary mode through which expression quantitative trait loci (eQTLs) are mediated. We further demonstrate that strain variation in chromatin state, paired with gene expression is useful for annotation of functional regions of the mouse genome. Finally, we provide a data resource that documents variation in chromatin state across genetically distinct individuals.
2022-09-25 | GSE213965 | GEO
Project description:It is well established that epigenetic features, such as histone modifications and DNA methylation, are associated with gene expression across cell types. However, it is not well known how variation in genotype affects epigenetic state, or to what extent such variation contributes to variation in gene expression across genetically distinct individuals. Here we investigated the relationship between heritable epigenetic variation and gene expression in hepatocytes across nine inbred mouse strains. Eight of the inbred strains were founders of the diversity outbred (DO) mice, and the ninth was DBA/2J, which, along with C57BL/6J, is one of the founders of the BxD recombinant inbred panel of mice. We surveyed four histone modifications, H3K4me1, H3K4me3, H3K27me3 and H3K27ac, as well as DNA methylation. We used ChromHMM to identify 14 chromatin states representing distinct combinations of the four measured histone modifications. We found that variation in chromatin state mirrored genetic variation across the inbred strains. Furthermore, epigenetic variation was correlated with gene expression across strains. The correspondence between epigenetic state and gene expression was replicated in an independent population of DO mice in which we imputed local epigenetic state. In contrast, we found that DNA methylation did not vary across inbred strains and was not correlated with variation in expression in DO mice. This work suggests that chromatin state is highly influenced by local genotype and may be a primary mode through which expression quantitative trait loci (eQTLs) are mediated. We further demonstrate that strain variation in chromatin state, paired with gene expression is useful for annotation of functional regions of the mouse genome. Finally, we provide a data resource that documents variation in chromatin state across genetically distinct individuals.
2022-09-25 | GSE213967 | GEO
Project description:It is well established that epigenetic features, such as histone modifications and DNA methylation, are associated with gene expression across cell types. However, it is not well known how variation in genotype affects epigenetic state, or to what extent such variation contributes to variation in gene expression across genetically distinct individuals. Here we investigated the relationship between heritable epigenetic variation and gene expression in hepatocytes across nine inbred mouse strains. Eight of the inbred strains were founders of the diversity outbred (DO) mice, and the ninth was DBA/2J, which, along with C57BL/6J, is one of the founders of the BxD recombinant inbred panel of mice. We surveyed four histone modifications, H3K4me1, H3K4me3, H3K27me3 and H3K27ac, as well as DNA methylation. We used ChromHMM to identify 14 chromatin states representing distinct combinations of the four measured histone modifications. We found that variation in chromatin state mirrored genetic variation across the inbred strains. Furthermore, epigenetic variation was correlated with gene expression across strains. The correspondence between epigenetic state and gene expression was replicated in an independent population of DO mice in which we imputed local epigenetic state. In contrast, we found that DNA methylation did not vary across inbred strains and was not correlated with variation in expression in DO mice. This work suggests that chromatin state is highly influenced by local genotype and may be a primary mode through which expression quantitative trait loci (eQTLs) are mediated. We further demonstrate that strain variation in chromatin state, paired with gene expression is useful for annotation of functional regions of the mouse genome. Finally, we provide a data resource that documents variation in chromatin state across genetically distinct individuals.
2022-09-25 | GSE213966 | GEO
Project description:Inbred individuals reared in controlled environments display considerable variance in many complex traits. The underlying cause of this variability has been an enigma, hence the term intangible variation. Here we show that two modifiers of epigenetic gene silencing play a critical role in the process. Inbred mice heterozygous for a null mutation in DNA methyltransferase 3a (Dnmt3a) or tripartite motif protein 28 (Trim28), show greater coefficients of variance in body weight than their wildtype littermates. Inbred mice carrying a mutation in Trim28 develop metabolic syndrome and abnormal behaviour with incomplete penetrance. These studies provide a molecular explanation of developmental noise in whole organisms and suggest that faithful epigenetic control of transcription is central to suppressing deleterious levels of phenotypic variation. These findings have broad implications for understanding the mechanisms underlying sporadic and complex disease in humans. Liver gene expression in Trim28MommeD9 heterozygotes compared to wildtype littermates.
2010-11-15 | E-GEOD-23512 | biostudies-arrayexpress