Transcriptomic and epigenomics atlas of myotubes reveals insight into the circadian control of metabolism and development [RRBS]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE131843 | GEO | 2020/03/11
REPOSITORIES: GEO
Similar Datasets
Project description:Aim: Innate circadian rhythms are critical for optimal tissue-specific functions, including skeletal muscle, a major insulin-sensitive tissue responsible for glucose homeostasis. We determined whether transcriptional oscillations are associated with CpG methylation changes in skeletal muscle. Materials & methods: We performed rhythmicity analysis on the transcriptome and CpG methylome of circadian synchronized myotubes. Results: We identified several transcripts and CpG-sites displaying oscillatory behavior, which were enriched with GO terms related to metabolism and development. Oscillating CpG methylation was associated with rhythmic expression of 31 transcripts. Conclusion: Although circadian oscillations may be regulated by rhythmic DNA methylation, strong rhythmic associations between transcriptome and CpG methylation were not identified. This resource constitutes a transcriptomic/epigenomic atlas of skeletal muscle and regulation of circadian rhythms.
2020-03-11 | GSE131842 | GEO
Project description:Circadian rhythms are cell-autonomous biological oscillations with a period of about 24 hours. Current models propose that transcriptional feedback loops are the principal mechanism for the generation of circadian oscillations. In these models, Drosophila S2 cells are generally regarded as ‘non-rhythmic’ cells, as they do not express several canonical circadian components. Using an unbiased multi-omics approach, we made the surprising discovery that Drosophila S2 cells do in fact display widespread daily rhythms. Transcriptomics and proteomics analyses revealed that hundreds of genes and their products are rhythmically expressed in a 24-hour cycle. Metabolomics analyses extended these findings and illustrated that central carbon metabolism and amino acid metabolism are the main pathways regulated in a rhythmic fashion. We thus demonstrate that daily genome-wide oscillations, coupled to metabolic cycles, take place in eukaryotic cells without the contribution of known circadian regulators.
2018-07-31 | PXD007669 | Pride
Project description:Rhythmic oscillations of physiological processes depend on integrating the circadian clock and diurnal environment. DNA methylation is epigenetically responsive to daily rhythms, as a subset of CpG dinucleotides in brain exhibit diurnal rhythmic methylation. A major genetic effect on rhythmic methylation was identified in a mouse Snord116 deletion model of the imprinted disorder Prader-Willi syndrome (PWS). > 23,000 diurnally rhythmic CpGs were identified in wild-type cortex, with nearly all lost or phase-shifted in PWS. Circadian dysregulation of a second imprinted Snord cluster at the Temple/Kagami-Ogata syndrome locus was observed at the level of methylation, transcription, and chromatin, providing mechanistic evidence of cross-talk. Genes identified by diurnal epigenetic changes in PWS mice overlapped rhythmic and PWS-specific genes in human brain and were enriched for PWS-relevant phenotypes and pathways. These results support the proposed evolutionary relationship between imprinting and sleep, and suggest possible chronotherapy in the treatment of PWS and related disorders.
2018-02-27 | GSE103249 | GEO
Project description:Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. While rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in wild-type and Bmal1 deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic genes expression, Bmal1 deletion having surprisingly more impact at the post-transcriptional level. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5â-TOP sequences and for genes involved in mitochondrial activity and harboring a TISU motif. The increased translation efficiency of 5â-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion impacts also amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. RNA-Seq from total RNA of mouse liver during the dirunal cycle. Time-series mRNA profiles of wild type (WT) and Bmal -/- mice under ad libitum and night restriced feeding regimen were generated by deep sequencing.
2015-11-10 | E-GEOD-73552 | biostudies-arrayexpress
Project description:Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. While rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in wild-type and Bmal1 deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic genes expression, Bmal1 deletion having surprisingly more impact at the post-transcriptional level. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5’-TOP sequences and for genes involved in mitochondrial activity and harboring a TISU motif. The increased translation efficiency of 5’-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion impacts also amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation.
2015-11-10 | GSE73553 | GEO
Project description:Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. While rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in wild-type and Bmal1 deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic genes expression, Bmal1 deletion having surprisingly more impact at the post-transcriptional level. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5’-TOP sequences and for genes involved in mitochondrial activity and harboring a TISU motif. The increased translation efficiency of 5’-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion impacts also amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation.
2015-11-10 | GSE73552 | GEO
Project description:<p>Circadian clocks coordinate mammalian behaviour and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.</p><p><br></p><p><strong>GC-MS assay</strong> protocols and data are reported in the current study <strong>MTBLS1286</strong>.</p><p><strong>LC-MS assay</strong> protocols and data for this study are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1285' rel='noopener noreferrer' target='_blank'><strong>MTBLS1285</strong></a>.</p>
2020-11-13 | MTBLS1286 | MetaboLights
Project description:<p>Circadian clocks coordinate mammalian behaviour and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.</p><p><br></p><p><strong>LC-MS assay</strong> protocols and data are reported in the current study <strong>MTBLS1285</strong>.</p><p><strong>GC-MS assay</strong> protocols and data for this study are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1286' rel='noopener noreferrer' target='_blank'><strong>MTBLS1286</strong></a>.</p>
2020-11-13 | MTBLS1285 | MetaboLights
Project description:To characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional “rush hours” preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more spliceforms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy. 96 samples total covering 12 different tissues, with no replicates. Each tissue sampled every 6 hours for 2 days (8 samples per tissue).
2014-09-30 | E-GEOD-54651 | biostudies-arrayexpress
Project description:To characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional “rush hours” preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more spliceforms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy. 288 samples total covering 12 different tissues, with no replicates. Each tissue sampled every 2 hours for 2 days (24 samples per tissue).
2014-09-30 | E-GEOD-54650 | biostudies-arrayexpress