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Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE64395 | GEO | 2015/06/30

SECONDARY ACCESSION(S): PRJNA270883

REPOSITORIES: GEO

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Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes.

Project description:ObjectiveTo examine the genome-wide distribution of hydroxymethylated cytosine (5hmC) in osteoarthritic (OA) and normal chondrocytes in order to investigate the effect on OA-specific gene expression.MethodsCartilage was obtained from OA patients undergoing total knee arthroplasty or from control patients undergoing anterior cruciate ligament reconstruction. Genome-wide sequencing of 5hmC-enriched DNA was performed in a small cohort of normal and OA chondrocytes to identify differentially hydroxymethylated regions (DhMRs) in OA chondrocytes. Data from the genome-wide sequencing of 5hmC-enriched DNA were intersected with global OA gene expression data to define subsets of genes and pathways potentially affected by increased 5hmC levels in OA chondrocytes.ResultsA total of 70,591 DhMRs were identified in OA chondrocytes as compared to normal chondrocytes, 44,288 (63%) of which were increased in OA chondrocytes. The majority of DhMRs (66%) were gained in gene bodies. Increased DhMRs were observed in ∼50% of genes previously implicated in OA pathology including MMP3, LRP5, GDF5, and COL11A1. Furthermore, analyses of gene expression data revealed gene body gain of 5hmC appears to be preferentially associated with activated, but not repressed, genes in OA chondrocytes.ConclusionThis study provides the first genome-wide profiling of 5hmC distribution in OA chondrocytes. We had previously reported a global increase in 5hmC levels in OA chondrocytes. Gain of 5hmC in the gene body is found to be characteristic of activated genes in OA chondrocytes, highlighting the influence of 5hmC as an epigenetic mark in OA. In addition, this study identifies multiple OA-associated genes that are potentially regulated either singularly by gain of DNA hydroxymethylation or in combination with loss of DNA methylation.

| S-EPMC4519426 | biostudies-literature

Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes [methylation]

2015-06-30 | GSE64393 | GEO

Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes [methylation]

2015-06-30 | E-GEOD-64393 | biostudies-arrayexpress

Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes [expression]

Project description:Examination of the genome-wide distribution of 5hmC in osteoarthritic chondrocytes compared to normal chondrocytes in order to elucidate the effect on OA-specific gene expression. 5hmC-sequencing was performed and data was compared with microarray gene expression data to identify genes with differential expression between normal and OA chondrocytes that are potentially under epigenetic regulation. Gene expression patterns were examined by comparing the 5 normal samples to the 2 OA samples to assess the changing expression profiles between normal and OA chondrocytes. We analyzed the changes in gene expression in OA; genes with a fold-change ≥ or ≤1.5 or 1.2, with a difference in intensity of >100 and within the lower 90% confidence bound, were selected.

2015-06-30 | E-GEOD-64394 | biostudies-arrayexpress

Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes [expression]

2015-06-30 | GSE64394 | GEO

Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes

Project description:Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes

| PRJNA270883 | ENA

Genome wide-DNA methylation analysis of articular chondrocytes reveals a cluster of osteoarthritic patients

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-04-01 | E-GEOD-43270 | biostudies-arrayexpress

Genome wide-DNA methylation analysis of articular chondrocytes reveals a cluster of osteoarthritic patients (methylation)

Project description:The aim of this study is to identify, for the first time, the genome-wide DNA methylation profiles of human articular chondrocytes from OA and healtly cartilage samples. Genome wide DNA methylation profiling of normal and osteoarthritic samples. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in cartilage knee samples. Samples included 18 healthy controls and 23 OA patients.

2013-04-01 | GSE43269 | GEO

Genome wide-DNA methylation analysis of articular chondrocytes reveals a cluster of osteoarthritic patients

Project description:This SuperSeries is composed of the SubSeries listed below.

2013-04-01 | GSE43270 | GEO

A genome-wide profiling of brain DNA hydroxymethylation in Alzheimer's disease.

Project description:IntroductionDNA methylation is a key epigenetic mechanism in brain aging and Alzheimer's disease (AD). The newly discovered 5-hydroxymethylcytosine mediates DNA demethylation, is highly abundant in the brain, and is dynamically regulated by life experiences. However, little is known about its genome-wide patterns and potential role in AD.MethodsUsing a genome-wide capture followed by high-throughput sequencing, we studied the genome-wide distribution of 5-hydroxymethylcytosine at specific genomic loci in human AD brain and identified differentially hydroxymethylated regions (DhMRs) associated with AD pathology.ResultsWe identified 517 DhMRs significantly associated with neuritic plaques and 60 DhMRs associated with neurofibrillary tangles. DNA hydroxymethylation in gene bodies was predominantly positively correlated with cis-acting gene expression. Moreover, genes showing differential hydroxymethylation were significantly enriched in neurobiological processes and clustered in functional gene ontology categories.DiscussionOur results reveal a critical role of DNA hydroxymethylation in AD pathology and provide mechanistic insight into the molecular mechanisms underlying AD.

| S-EPMC6675576 | biostudies-literature

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