Similar Datasets
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 | 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 | GSE213966 | GEO
Project description:Variation in histone configurations correlates with gene expression across nine inbred strains of mice
| PRJNA883381 | ENA
Project description:Variation in histone configurations correlates with gene expression across nine inbred strains of mice [RRBS]
| PRJNA883385 | ENA
Project description:Variation in histone configurations correlates with gene expression across nine inbred strains of mice [ChIP-seq]
| PRJNA883387 | ENA
Project description:Variation in histone configurations correlates with gene expression across nine inbred strains of mice [RNA-seq]
| PRJNA883383 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2010-12-31 | GSE24643 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2014-12-01 | GSE53006 | GEO
Project description:Studies in mice suggest that rapamycin has a negative impact on glucose homeostasis by inducing insulin resistance. However, results have been inconsistent and difficult to assess because the strains, methods of treatment, and analysis vary among studies. Using a consistent protocol, we surveyed nine inbred strains of mice for the effect of rapamycin on various aspects of glucose metabolism. Across all strains, rapamycin significantly delayed glucose clearance after challenge. However, rapamycin showed no main effect on systemic insulin sensitivity. Analysis of individual strains shows that rapamycin induced higher glucose values at 15 minutes post-challenge in 7/9 strains. However, only three strains show rapamycin-induced reduction in glucose clearance from 15 to 120 minutes. Although pancreatic insulin content was reduced by rapamycin in seven strains, none showed reduced serum insulin values. Although one strain showed no effects of rapamycin on glucose metabolism (129), another showed increased systemic insulin sensitivity (B6). We suggest that rapamycin likely inhibits insulin production and secretion in most strains while having strain-specific effects on glucose clearance without altering systemic insulin sensitivity. This strain survey indicates that genetic differences greatly influence the metabolic response to rapamycin.
| S-EPMC6909913 | biostudies-literature