Development of a novel aging clock based on chromatin accessibility [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA795126 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17465600_1.fastq.gz | Fastqsanger.gz | |||
| SRR17465600_2.fastq.gz | Fastqsanger.gz | |||
| SRR17465601_1.fastq.gz | Fastqsanger.gz | |||
| SRR17465601_2.fastq.gz | Fastqsanger.gz | |||
| SRR17465602_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 318 |
Similar Datasets
Project description:The establishment of highly accurate aging clocks based on DNA methylation highlighted the strong link between epigenetic alterations and aging. However, connecting methylation clocks to physiological changes is not straightforward. Transcriptomics and proteomics clocks on the other hand are directly connected to cellular function, yet they do not allow us to understand underlying epigenetic mechanisms. We hypothesize that chromatin accessibility, a readout that integrates many epigenetic mechanisms, may bridge epigenetic changes with their downstream effects in aging. To demonstrate that chromatin accessibility can predict age, we generated chromatin accessibility profiles from peripheral blood mononuclear cells (PBMCs) of 157 human donors, aged 20 to 74 and used them to construct a novel aging clock. Our clock predicted age with a root mean squared error of 7.69 years, a median absolute error of 5.69 years and a correlation of 0.83. Moreover, by comparing our chromatin accessibility data to matched transcriptomic profiles, we show that the genomic sites selected by our clock drive changes in transcription during aging. This chromatin accessibility clock could therefore be used to better understand the mechanisms driving the process of aging and evaluate anti-aging interventions.
2022-12-01 | GSE193141 | GEO
Project description:The establishment of highly accurate aging clocks based on DNA methylation highlighted the strong link between epigenetic alterations and aging. However, connecting methylation clocks to physiological changes is not straightforward. Transcriptomics and proteomics clocks on the other hand are directly connected to cellular function, yet they do not allow us to understand underlying epigenetic mechanisms. We hypothesize that chromatin accessibility, a readout that integrates many epigenetic mechanisms, may bridge epigenetic changes with their downstream effects in aging. To demonstrate that chromatin accessibility can predict age, we generated chromatin accessibility profiles from peripheral blood mononuclear cells (PBMCs) of 157 human donors, aged 20 to 74 and used them to construct a novel aging clock. Our clock predicted age with a root mean squared error of 7.69 years, a median absolute error of 5.69 years and a correlation of 0.83. Moreover, by comparing our chromatin accessibility data to matched transcriptomic profiles, we show that the genomic sites selected by our clock drive changes in transcription during aging. This chromatin accessibility clock could therefore be used to better understand the mechanisms driving the process of aging and evaluate anti-aging interventions.
2022-12-01 | GSE193140 | GEO
Project description:Development of a novel aging clock based on chromatin accessibility
| PRJNA795114 | ENA
Project description:Development of a novel aging clock based on chromatin accessibility [ATAC-seq]
| PRJNA795127 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-12-01 | GSE193142 | GEO
Project description:The establishment of aging clocks highlighted the strong link between changes in DNA methylation and aging. Yet, it is not known if other epigenetic features could be used to predict age accurately. Furthermore, previous studies have observed a lack of effect of age-related changes in DNA methylation on gene expression, putting the interpretability of DNA methylation-based aging clocks into question. In this study, we explore the use of chromatin accessibility to construct aging clocks. We collected blood from 159 human donors and generated chromatin accessibility, transcriptomic, and cell composition data. We investigated how chromatin accessibility changes during aging and constructed a novel aging clock with a median absolute error of 5.27 years. The changes in chromatin accessibility used by the clock were strongly related to transcriptomic alterations, aiding clock interpretation. We additionally show that our chromatin accessibility clock performs significantly better than a transcriptomic clock trained on matched samples. In conclusion, we demonstrate that the clock relies on cell-intrinsic chromatin accessibility alterations rather than changes in cell composition. Further, we present a new approach to construct epigenetic aging clocks based on chromatin accessibility, which bear a direct link to age-related transcriptional alterations, but which allow for more accurate age predictions than transcriptomic clocks.
| S-EPMC10828344 | biostudies-literature
Project description:Chromatin organization plays a crucial role in gene regulation by controlling the accessibility of DNA to transcription machinery. While significant progress has been made in understanding the regulatory role of clock proteins in circadian rhythms, how chromatin organization affects circadian rhythms remains poorly understood. Here, we employed ATAC-seq (Assay for Transposase-Accessible Chromatin with Sequencing) on FAC-sorted Drosophila clock neurons to assess genome-wide chromatin accessibility at dawn and dusk over the circadian cycle. We observed significant oscillations in chromatin accessibility at promoter and enhancer regions of hundreds of genes, with enhanced accessibility either at dusk or dawn, which correlated with their peak transcriptional activity. Notably, genes with enhanced accessibility at dusk were enriched with E-box motifs, while those more accessible at dawn were enriched with VRI/PDP1-box motifs, indicating that they are regulated by the core circadian feedback loops, PER/CLK and VRI/PDP1, respectively. Further, we observed a complete loss of chromatin accessibility rhythms in per01 null mutants, with chromatin consistently accessible at both dawn and dusk, underscoring the critical role of Period protein in driving chromatin compaction during the repression phase at dawn. Together, this study demonstrates the significant role of chromatin organization in circadian regulation, revealing how the interplay between clock proteins and chromatin structure orchestrates the precise timing of biological processes throughout the day. This work further implies that variations in chromatin accessibility might play a central role in the generation of diverse circadian gene expression patterns in clock neurons.
2024-03-05 | GSE256533 | GEO
Project description:Sirtuin 1 (SIRT1) is involved in both aging and circadian-clock regulation, yet the link between the two processes in relation to SIRT1 function is not clear. Using Sirt1-deficient mice, we found that Sirt1 and Period 2 (Per2) constitute a reciprocal negative regulation loop that plays important roles in modulating hepatic circadian rhythmicity and aging. Sirt1-deficient mice exhibited profound premature aging and enhanced acetylation of histone H4 on lysine16 (H4K16) in the promoter of Per2, the latter of which leads to its overexpression; in turn, Per2 suppresses Sirt1 transcription through binding to the Sirt1 promoter at the Clock/Bmal1 site. This negative reciprocal relationship between SIRT1 and PER2 was also observed in human hepatocytes. We further demonstrated that the absence of Sirt1 or the ectopic overexpression of Per2 in the liver resulted in a dysregulated pace of the circadian rhythm. The similar circadian rhythm was also observed in aged wild type mice. The interplay between Sirt1 and Per2 modulates aging gene expression and circadian-clock maintenance. To investigate hepatic SIRT1-dependent aging related genes, livers from wild type mice at 3 months (young), 12 months (middle age), and 19 months (old) of age, as well as Sirt1-deficient mice at 3 months of age were snap frozen and subject to RNA isolation and microarray analysis.
2016-08-08 | E-GEOD-54436 | biostudies-arrayexpress
Project description:Clock-dependent chromatin accessibility rhythms regulate circadian transcription
| PRJNA1079999 | ENA
Project description:Regulation of gene expression is linked to the organization of the genome. With age, chromatin alterations occur on all levels of genome organization, accompanied by changes in the gene expression profile. However, little is known about the changes on the level of transcriptional regulation. Here, we used a multi-omics approach and integrated ATAC-, RNA- and NET-seq to identify age-related changes in the chromatin landscape of murine liver and to investigate how these are linked to transcriptional regulation. We provide the first systematic inventory of the connection between aging, chromatin accessibility and transcriptional regulation in a whole tissue. Aging in murine liver is characterized by an increase in chromatin accessibility at promoter regions, but not in an increase of transcriptional output. Instead, aging is accompanied by a decrease of promoter-proximal pausing of RNA polymerase II (Pol II). We propose that these changes in transcriptional regulation are due to a reduced stability of the pausing complex and may represent a mechanism to compensate for the age-related increase in chromatin accessibility in order to prevent aberrant transcription.
2022-09-15 | PXD034564 | Pride