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DNA Methyltransferase inhibition reverses epigenetically embedded phenotypes in lung cancer preferentially affecting Polycomb target genes

ABSTRACT: Cancer cell phenotypes are partially determined by epigenetic specifications such as DNA methylation. Metastasis development is a late event in cancerogenesis and might be associated with epigenetic alterations. Here, we analyzed genome wide DNA methylation changes that were associated with pro-metastatic phenotypes in non-small cell lung cancer with Reduced Representation Bisulfite Sequencing. DNMT-inhibition by 5-Azacytidine at low concentrations reverted the pro-metastatic phenotype. 5-Azacytidine led to preferential loss of DNA methylation at sites that were DNA hypermethylated during the in vivo selection. Changes in DNA methylation persisted over time.

ORGANISM(S): Homo sapiens

PROVIDER: GSE44390 | GEO | 2013/12/18

SECONDARY ACCESSION(S): PRJNA189722

REPOSITORIES: GEO

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DNA Methyltransferase inhibition reverses epigenetically embedded phenotypes in lung cancer preferentially affecting Polycomb target genes

2013-12-18 | E-GEOD-44390 | biostudies-arrayexpress

Examination of genome-wide methylation changes in lung cancer cell lines A549 (A) and HTB56 (H) [RRBS-Seq experiments]

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Examination of genome-wide methylation changes in lung cancer cell lines A549 (A) and HTB56 (H) [RRBS-Seq experiments]

Project description:Cancer cell phenotypes are partially determined by epigenetic specifications such as DNA methylation. Metastasis development is a late event in cancerogenesis and might be associated with epigenetic alterations. Here, we analyzed genome wide DNA methylation changes that were associated with pro-metastatic phenotypes in non-small cell lung cancer with Reduced Representation Bisulfite Sequencing. DNMT-inhibition by 5-Azacytidine at low concentrations reverted the pro-metastatic phenotype. 5-Azacytidine led to preferential loss of DNA methylation at sites that were DNA hypermethylated during the in vivo selection. Changes in DNA methylation persisted over time. Keywords: Methylation profiling by high throughput sequencing We studied genome-wide methylation changes in lung cancer cell lines A549 (A) and HTB56 (H). We generated NSCLC lines with highly increased propensity to form tumor nodules in murine lungs after intravenous injections. In addition to the normal cell lines (0R) we analyzed the methylome of the the cell lines after three rounds of in vivo selection towards a highly metastatic phenotype (3R). Next we studied changes in the methylome of highly metastatic cell lines after DNA Methyltransferase inhibition by 5-Azacytidine treatment at low concentrations (250 nM & 1000 nM) for 6 days. During treatment cells were supplemented with fresh medium every 48 hours. After 6 days of 5-Azacytidine exposure, cells were washed three times with PBS to wash out the drug. The cells were released for additional 7 days in regular medium. We followed up the DNA methylation changes at day 13 of the experiment.

2013-12-18 | E-GEOD-52140 | biostudies-arrayexpress

Examination of genome-wide methylation changes in lung cancer cell lines A549 (A) and HTB56 (H) [HumanMethylation27 BeadChip experiments]

2013-12-18 | GSE52144 | GEO

Examination of genome-wide methylation changes in lung cancer cell lines A549 (A) and HTB56 (H) [HumanMethylation27 BeadChip experiments]

2013-12-18 | E-GEOD-52144 | biostudies-arrayexpress

Homo sapiens

Project description:Aberrant BAF57 Signaling Facilitates Pro-metastatic Phenotypes

| PRJNA189937 | ENA

DNA methylation profiling in chondrocyte dedifferentiation in vitro

Project description:Genome wide DNA methylation profiling of different passages of human articular chondrocytes treated with 5-azacytidine. The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,578 CpGs.Samples included 6 different passages of human articular chondrocytes with 5-azacytidine treatment, 6 different passages without 5-azacytidine treatment,

2015-01-31 | GSE65467 | GEO

DNA methylation profiling in chondrocyte dedifferentiation in vitro

2015-01-31 | E-GEOD-65467 | biostudies-arrayexpress

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Project description:DNA microarray experiments were used to compare gene expression profiles of untreated and 5-azacytidine treated Escherichia coli at both logarithmic phase and early stationary phase The goal was to determine the effect of cytosine DNA methylation loss on gene expression (5-azacytidine is a methylation inhibitor)

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A comparative analysis of 5-azacytidine and zebularine induced DNA demethylation using whole-genome bisulfite sequencing

Project description:The non-methylable cytosine analogs, 5-azacytidine and zebularine, are widely used to disrupt DNA methyltransferase activity and reduce genomic DNA methylation. In this study, whole-genome bisulfite sequencing is used to construct maps of DNA methylation with single base pair resolution in Arabidopsis thaliana seedlings treated with each demethylating agent. We find that 5-azacytidine and zebularine-treated seedlings have nearly indistinguishable patterns of DNA methylation genome-wide and that 5-azacytidine, despite being more unstable in aqueous solution, has a slightly greater demethylating effect at higher concentrations across the genome. Transcriptome analyses revealed a substantial number of up-regulated genes and transposable element genes, particularly CACTA-like elements, demonstrating that chemical demethylating agents have a disproportionately large effect on loci that are silenced by DNA methylation. Bisulfite-Seq and RNA-Seq

2016-06-24 | E-GEOD-80300 | biostudies-arrayexpress

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