Interplay between Genetic Variation and Nutrition Challenge Controls Hepatic Diurnal Rhythms [ChIP-seq]
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PROVIDER: PRJNA1169621 | ENA |
REPOSITORIES: ENA
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Project description:Interplay between Genetic Variation and Nutrition Challenge Controls Hepatic Diurnal Rhythms [RNA-seq]
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Project description:Variation in diurnal rhythms contributes to the risk of multiple diseases, yet the genomic and epigenomic basis remains largely unknown. Here, we show that SNPs in enhancer and promoter regions genome-wide contribute to variations in human diurnal rhythms. Differential rhythmic gene expression and physiological responses to diet-induced obesity in mice with different genetic backgrounds are linked to time-dependent enhancer-promoter interactions (EPI) regulated by cis-regulatory SNPs and transcription factors (TFs) like ESRRγ. Hepatocyte-specific Esrrγ knockout alters rhythmic processes in liver, including triglyceride synthesis and lipid droplet formation, across mouse strains. Moreover, motifs of ESRRγ and other lipid metabolism-related TFs are enriched in individual-specific EPIs harboring SNPs to control rhythmic genes in patients with MAFLD. SNPs located in these sites are correlated with hepatic metabolic traits. Thus, SNPs and TFs interdependently form the genomic and epigenomic basis for diurnal rhythm variation, contributing to disease risk.
2025-08-25 | GSE278920 | GEO
Project description:Variation in diurnal rhythms contributes to the risk of multiple diseases, yet the genomic and epigenomic basis remains largely unknown. Here, we show that SNPs in enhancer and promoter regions genome-wide contribute to variations in human diurnal rhythms. Differential rhythmic gene expression and physiological responses to diet-induced obesity in mice with different genetic backgrounds are linked to time-dependent enhancer-promoter interactions (EPI) regulated by cis-regulatory SNPs and transcription factors (TFs) like ESRRγ. Hepatocyte-specific Esrrγ knockout alters rhythmic processes in liver, including triglyceride synthesis and lipid droplet formation, across mouse strains. Moreover, motifs of ESRRγ and other lipid metabolism-related TFs are enriched in individual-specific EPIs harboring SNPs to control rhythmic genes in patients with MAFLD. SNPs located in these sites are correlated with hepatic metabolic traits. Thus, SNPs and TFs interdependently form the genomic and epigenomic basis for diurnal rhythm variation, contributing to disease risk.
2025-08-25 | GSE297115 | GEO
Project description:Variation in diurnal rhythms contributes to the risk of multiple diseases, yet the genomic and epigenomic basis remains largely unknown. Here, we show that SNPs in enhancer and promoter regions genome-wide contribute to variations in human diurnal rhythms. Differential rhythmic gene expression and physiological responses to diet-induced obesity in mice with different genetic backgrounds are linked to time-dependent enhancer-promoter interactions (EPI) regulated by cis-regulatory SNPs and transcription factors (TFs) like ESRRγ. Hepatocyte-specific Esrrγ knockout alters rhythmic processes in liver, including triglyceride synthesis and lipid droplet formation, across mouse strains. Moreover, motifs of ESRRγ and other lipid metabolism-related TFs are enriched in individual-specific EPIs harboring SNPs to control rhythmic genes in patients with MAFLD. SNPs located in these sites are correlated with hepatic metabolic traits. Thus, SNPs and TFs interdependently form the genomic and epigenomic basis for diurnal rhythm variation, contributing to disease risk.
2025-08-25 | GSE278921 | GEO
Project description:Variation in diurnal rhythms contributes to the risk of multiple diseases, yet the genomic and epigenomic basis remains largely unknown. Here, we show that SNPs in enhancer and promoter regions genome-wide contribute to variations in human diurnal rhythms. Differential rhythmic gene expression and physiological responses to diet-induced obesity in mice with different genetic backgrounds are linked to time-dependent enhancer-promoter interactions (EPI) regulated by cis-regulatory SNPs and transcription factors (TFs) like ESRRγ. Hepatocyte-specific Esrrγ knockout alters rhythmic processes in liver, including triglyceride synthesis and lipid droplet formation, across mouse strains. Moreover, motifs of ESRRγ and other lipid metabolism-related TFs are enriched in individual-specific EPIs harboring SNPs to control rhythmic genes in patients with MAFLD. SNPs located in these sites are correlated with hepatic metabolic traits. Thus, SNPs and TFs interdependently form the genomic and epigenomic basis for diurnal rhythm variation, contributing to disease risk.
2025-08-25 | GSE278922 | GEO
Project description:RAW spectrum files associated with "DIURNAL RHYTHMS SPATIALLY AND TEMPORALLY ORGANIZE AUTOPHAGY"
2019-01-15 | MSV000083314 | MassIVE
Project description:The human striatum can be subdivided into the caudate, putamen, and nucleus accumbens (NAc). Each of these structures have some overlapping and some distinct functions related to motor control, cognitive processing, motivation, and reward. Previously, we used a “time of death” approach to identify diurnal rhythms in RNA transcripts in human cortical regions. Here, we identify molecular rhythms across the three striatal subregions collected from postmortem human brain tissue in subjects without psychiatric or neurological disorders. Core circadian clock genes are rhythmic across all three regions and show strong phase concordance across regions. However, the putamen contains a much larger number of significantly rhythmic transcripts than the other two regions. Moreover, there are many differences in pathways that are rhythmic across regions. Strikingly, the top rhythmic transcripts in NAc (but not the other regions) are predominantly snoRNAs and lncRNAs, suggesting that a completely different mechanism might be used for the regulation of diurnal rhythms in translation and/or RNA processing in the NAc versus the other regions. Further, although the NAc and putamen are generally in phase with regards to timing of expression rhythms, the NAc and caudate, and caudate and putamen, have several clusters of discordant rhythmic transcripts, suggesting a temporal wave of specific cellular processes with the caudate preceding the other regions. Taken together, these studies reveal distinct transcriptome rhythms across the human striatum and are an important step in helping to understand the normal function of diurnal rhythms in these regions and how disruption could lead to pathology.
2020-12-31 | GSE160521 | GEO
Project description:Circadian rhythmicity is a defining feature of mammalian metabolism that synchronizes metabolic processes to day-night light cycles. Here, we show that the intestinal microbiota programs diurnal metabolic rhythms in the mouse small intestine through histone deacetylase 3 (HDAC3). The microbiota induced expression of intestinal epithelial HDAC3, which was recruited rhythmically to chromatin and produced synchronized diurnal oscillations in histone acetylation, metabolic gene expression, and nutrient uptake. HDAC3 also functioned non-canonically to coactivate estrogen related receptor a (ERRa), inducing microbiota-dependent rhythmic transcription of the lipid transporter gene Cd36 and promoting lipid absorption and diet-induced obesity. Our findings reveal that HDAC3 integrates microbial and circadian cues to regulate diurnal metabolic rhythms, and pinpoint a key mechanism by which the microbiota controls host metabolism.
2019-09-26 | GSE134303 | GEO