A high-fat diet alters genome-wide DNA methylation and gene expression in SM/J mice

Abstract

BackgroundWhile the genetics of obesity has been well defined, the epigenetics of obesity is poorly understood. Here, we used a genome-wide approach to identify genes with differences in both DNA methylation and expression associated with a high-fat diet in mice.ResultsWe weaned genetically identical Small (SM/J) mice onto a high-fat or low-fat diet and measured their weights weekly, tested their glucose and insulin tolerance, assessed serum biomarkers, and weighed their organs at necropsy. We measured liver gene expression with RNA-seq (using 21 total libraries, each pooled with 2 mice of the same sex and diet) and DNA methylation with MRE-seq and MeDIP-seq (using 8 total libraries, each pooled with 4 mice of the same sex and diet). There were 4356 genes with expression differences associated with diet, with 184 genes exhibiting a sex-by-diet interaction. Dietary fat dysregulated several pathways, including those involved in cytokine-cytokine receptor interaction, chemokine signaling, and oxidative phosphorylation. Over 7000 genes had differentially methylated regions associated with diet, which occurred in regulatory regions more often than expected by chance. Only 5–10% of differentially methylated regions occurred in differentially expressed genes, however this was more often than expected by chance (p = 2.2 × 10− 8).ConclusionsDiscovering the gene expression and methylation changes associated with a high-fat diet can help to identify new targets for epigenetic therapies and inform about the physiological changes in obesity. Here, we identified numerous genes with altered expression and methylation that are promising candidates for further study.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5327-0) contains supplementary material, which is available to authorized users.

Impact of 3D genome organization, guided by cohesin and CTCF looping, on sex-biased chromatin interactions and gene expression in mouse liver

“…Furthermore, many of these sex-biased binding sites are located in TADs without any known sex-biased genes. Although those sites lack any obvious link to sex-biased gene expression in untreated liver, they could have a priming effect and contribute to sex-specific responses reported for hepatic stressors, such as high fat diet [79] and xenobiotic exposure [80], which we recently showed can induce a sex-biased gene response in TADs whose genes do not show a sex-bias in expression in the unstressed state [81]. Just as short-term feeding of a high fat diet can leave a lasting epigenetic memory in the form of epigenetic modifications [82], sex-biased binding of CTCF and/or cohesin may differentially prime each sex for distinct looping patterns that enable the observed sex-biased responses to chemical exposure or dietary stressors.…”

Impact of 3D genome organization, guided by cohesin and CTCF looping, on sex-biased chromatin interactions and gene expression in mouse liver

“…Furthermore, many of these sex-biased binding sites are located in TADs without any known sex-biased genes. Although those sites lack any obvious link to sexbiased gene expression in untreated liver, they could have a priming effect and contribute to sex-speci c responses reported for hepatic stressors, such as high fat diet [80] and xenobiotic exposure [81], which we recently showed can induce a sex-biased gene response in TADs whose genes do not show a sex-bias in expression in the unstressed state [82]. Just as short-term feeding of a high fat diet can leave a lasting epigenetic memory in the form of epigenetic modi cations [83], sex-biased binding of CTCF and/or cohesin may differentially prime each sex for distinct looping patterns that enable the observed sexbiased responses to chemical exposure or dietary stressors.…”

Impact of 3D genome organization, guided by cohesin and CTCF looping, on sex-biased chromatin interactions and gene expression in mouse liver

“…Furthermore, fewer than half of these sex-biased binding sites are located in TADs with a known sex-biased gene. Although those sites lack any obvious link to sex-biased gene expression in untreated liver, they could have a priming effect and contribute to sex-specific responses reported for hepatic stressors, such as high fat diet [80] and xenobiotic exposure [81], which we recently showed can induce a sex-biased gene response in TADs whose genes do not show a sex-bias in expression in the unstressed state [82]. Just as short-term feeding of a high fat diet can leave a lasting epigenetic memory in the form of epigenetic modifications [83], sex-biased binding of CTCF and/or cohesin may differentially prime each sex for distinct looping patterns that enable the observed sex-biased responses to chemical exposure or dietary stressors.…”