Unknown,Transcriptomics,Genomics,Proteomics

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Epigenome analysis of fetal and adult liver samples

ABSTRACT: Genome wide DNA methylation analysis of 96 adult and 14 fetal liver samples The study includes 110 individuals, 14 fetal and 96 adult samples, no replicates. Liver samples from 14 fetuses were obtained at gestational week 8-12. Adult liver samples were collected from 52 organ donors who had met accidental death and 44 liver samples from patients undergoing liver resection due to malignant tumors, most commonly from patients with metastatic colon cancers. Liver biopsies from these patients were collected from 'healthy' tissue that showed no visible pathological changes compared to the adjacent tumor.

ORGANISM(S): Homo sapiens

SUBMITTER: Lili Milani

PROVIDER: E-GEOD-61278 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Aging is a progressive process that results in the accumulation of intra- and extracellular alterations that in turn contribute to a reduction in health. Age-related changes in DNA methylation have been reported before and may be responsible for aging-induced changes in gene expression, although a causal relationship has yet to be shown. Using genome-wide assays, we analyzed age-induced changes in DNA methylation and their effect on gene expression with and without transient induction with the synthetic transcription modulating agent WY14,643. To demonstrate feasibility of the approach, we isolated peripheral blood mononucleated cells (PBMCs) from five young and five old healthy male volunteers and cultured them with or without WY14,643. Infinium 450K BeadChip and Affymetrix Human Gene 1.1 ST expression array analysis revealed significant differential methylation of at least 5 % (M-NM-^TYOM-bM-^@M-^I>M-bM-^@M-^I5 %) at 10,625 CpG sites between young and old subjects, but only a subset of the associated genes were also differentially expressed. Age-related differential methylation of previously reported epigenetic biomarkers of aging including ELOVL2, FHL2, PENK, and KLF14 was confirmed in our study, but these genes did not display an age-related change in gene expression in PBMCs. Bioinformatic analysis revealed that differentially methylated genes that lack an age-related expression change predominantly represent genes involved in carcinogenesis and developmental processes, and expression of most of these genes were silenced in PBMCs. No changes in DNA methylation were found in genes displaying transiently induced changes in gene expression. In conclusion, aging-induced differential methylation often targets developmental genes and occurs mostly without change in gene expression. Peripheral blood mononuclear cells were isolated from 10 volunteers (5 young 5 old), treated with the synthetic PPARalpha agonists WY14,643 or control for 13 hrs, and subjected to genome-wide DNA methylation and gene expression analysis. This entry contains the DNA methylation data.

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Epigenome analysis of fetal and adult liver samples

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