H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE52114 | GEO | 2014/09/25
SECONDARY ACCESSION(S): PRJNA226709
REPOSITORIES: GEO
Similar Datasets
Project description:In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors.
| S-EPMC4317171 | biostudies-literature
Project description:In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone posttranslational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells obtained from individuals aged 2 to 92 identified 18735 hypermethylated and 45407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on non-genetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type and chromatin context involved, and that, depending on the locus, the changes can be modulated by genetic and/or external factors.
2014-09-25 | GSE52112 | GEO
Project description:In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone posttranslational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells obtained from individuals aged 2 to 92 identified 18735 hypermethylated and 45407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on non-genetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type and chromatin context involved, and that, depending on the locus, the changes can be modulated by genetic and/or external factors.
2014-09-25 | GSE52113 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-09-25 | E-GEOD-52114 | biostudies-arrayexpress
Project description:In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone posttranslational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells obtained from individuals aged 2 to 92 identified 18735 hypermethylated and 45407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on non-genetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type and chromatin context involved, and that, depending on the locus, the changes can be modulated by genetic and/or external factors. Total DNA isolated by standard procedures from peripheral blood of 24 samples obtained from 12 pairs of MZ twins aged 21 to 66.
2014-09-25 | E-GEOD-52113 | biostudies-arrayexpress
Project description:In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone posttranslational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells obtained from individuals aged 2 to 92 identified 18735 hypermethylated and 45407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on non-genetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type and chromatin context involved, and that, depending on the locus, the changes can be modulated by genetic and/or external factors. Total DNA isolated by standard procedures from human adult mesenchymal stem cells (MSCs) obtained from 34 individuals aged 2 to 92
2014-09-25 | E-GEOD-52112 | biostudies-arrayexpress
Project description:H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells
| PRJNA226709 | ENA
Project description:Temporal and spatial gene expression patterns are regulated by enhancer-specific histone modifications H3K4me1 and H3K27ac. To better understand age-dependent alteration of these enhancer marks, we analysed their genome-wide profiles and compared against changes in gene expression in the head tissues harvested from young Day 10 and D50 male Drosophila. The genome-wide binding patterns of H3K4me1 and H3K27ac remain highly similar (>85%) during ageing with marginally higher signals for both marks in older Day 50 flies. Signals were significantly higher in Day 50 flies near the transcription start sites for H3K4me1 whereas for H3K27ac, signals were significantly higher in Day 50 flies globally. Interestingly, analysis using MACS bdgdiff identified “x” H3K4me1 and “y” H3K27ac differential peaks that correlated with distinct sets of age-dependent differential expressed genes (DEG). Most of the H3K4me1 differential peaks (percentage of x) are located within the gene body of DEGs that are associated with RNA and metabolic processes. On the other hand, majority of differential H3K27ac peaks (percentage of y) are located 5 kb upstream of TSS of DEG enriched for various immune responses. Our results suggest that while both enhancer marks do not undergo significant global reconfiguration during aging, they are likely to be involved in activating independent sets of genes through distinct transcription activators.
2023-12-31 | GSE210427 | GEO
Project description:CpG dinucleotides are the main mutational hot-spot in most cancers. The characteristic elevated C>T mutation rate in CpG sites has been related to 5-methylcytosine (5mC), an epigenetically modified base which resides in CpGs and plays a role in transcription silencing. In brain nearly a third of 5mCs have recently been found to exist in the form of 5-hydroxymethylcytosine (5hmC), yet the effect of 5hmC on mutational processes is still poorly understood. Here we show that 5hmC is associated with an up to 53% decrease in the frequency of C>T mutations in a CpG context compared to 5mC. Tissue specific 5hmC patterns in brain, kidney and blood correlate with lower regional CpG>T mutation frequency in cancers originating in the respective tissues. Together our data reveal global and opposing effects of the two most common cytosine modifications on the frequency of cancer causing somatic mutations in different cell types.
| S-EPMC4931910 | biostudies-literature
Project description:The epigenetic inheritance relies on stability of histone marks, but various diseases, including aging-related disorders, are usually associated with alterations of histone marks. Whether and how the proteasome is responsible for maintaining the histone marks during transcription and aging remain unclear. The core histones can be degraded by the atypical proteasome, which contains the proteasome activator PA200, in an acetylation-dependent manner during somatic DNA damage response and spermiogenesis. Methods: By utilizing a substitute of methionine to label proteins metabolically, we analyzed histone degradation genome-wide by sequencing the DNA fragments following pulse-chase assays. The genome-wide RNA-sequencing analysis was performed to analyze transcription and chromatin-immunoprecipitation (ChIP)-sequencing was used for analyses of histone marks. The experimental models included gene-manipulated cells (including both mouse and yeast), mouse liver, and mice. Results: Degradation of H4 or the transcription-coupled histone variant H3.3 could be suppressed by deletion of PA200 or its yeast ortholog Blm10. The histone deacetylase inhibitor accelerated the degradation rates of H3, while the mutations of the putative acetyl-lysine-binding region of PA200 abolished histone degradation in the G1-arrested cells. Deletion of PA200 dramatically altered deposition of the active transcriptional hallmarks (H3K4me3 and H3K56ac) and transcription, especially during cellular aging. Furthermore, deletion of PA200 or Blm10 accelerated cellular aging. Notably, the PA200-deficient mice displayed a range of aging-related deteriorations, including immune malfunction, anxiety-like behavior and shorter lifespan. Conclusion: PA200 promotes the transcription-coupled degradation of the core histones, and plays an important role in maintaining the stability of histone marks during transcription and aging.
| S-EPMC7738882 | biostudies-literature