Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide profiling of PARP1 reveals an interplay with gene regulatory regions and DNA methylation

ABSTRACT: To address the global impact of PARP-1 on DNA methylation, we treated cells with PJ34 (PARylation inhibitor) and isolated genomic DNA from vehicle and PJ34 treated cells. This DNA was bisulfite treated and hybridized to the Illumina infinium Methylation 450 Beadchip. We next used these RNA-seq data sets (control, PARP-1 KD and PARylation inhibited) to assess whether PARP plays a role in DNA methylation by assessing differential methylation patterns. PARP1 mediates methylation patterns. DNA from vehicle and PJ34 (PARylation inhibited) cells. 750ng of geneomic DNA was bisulfite converted and used for the Illumia infinium HD methylation assay.

ORGANISM(S): Homo sapiens

SUBMITTER: Yvonne Fondufe-Mittendorf

PROVIDER: E-GEOD-61744 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Treatment with recombinant human growth hormone (rhGH) has been consistently reported to induce transcriptional changes in various human tissues including peripheral blood. For other hormones it has been shown that the induction of such transcriptional effects is conferred or at least accompanied by DNA-methylation changes. To analyse effects of short term rhGH treatment on the DNA-methylome we investigated a total of 24 patients at baseline and after 4-day rhGH stimulation. We performed array-based DNA-methylation profiling of paired peripheral blood mononuclear cell samples followed by targeted validation using bisulfite pyrosequencing. Unsupervised analysis of DNA-methylation in this short-term treated cohort revealed clustering according to individuals rather than treatment. Supervised analysis identified 239 CpGs as significantly differentially methylated between baseline and rhGH-stimulated samples (p<0.0001, unadjusted paired t-test), which nevertheless did not retain significance after adjustment for multiple testing. An individualised evaluation strategy led to the identification of 2350 CpG and 3 CpH sites showing methylation differences of at least 10% in more than 2 of the 24 analysed sample pairs. To investigate the long term effects of rhGH treatment on the DNA-methylome, we analysed peripheral blood cells from an independent cohort of 36 rhGH treated children born small for gestational age (SGA) as compared to 18 untreated controls. Median treatment interval was 33 months. In line with the groupwise comparison in the short-term treated cohort no differentially methylated targets reached the level of significance in the long-term treated cohort. We identified marked intra-individual responses of DNA-methylation to short-term rhGH treatment. These responses seem to be predominately associated with immunologic functions and show considerable inter-individual heterogeneity. The latter is likely the cause for the lack of a rhGH induced homogeneous DNA-methylation signature after short- and long-term treatment, which nevertheless is well in line with generally assumed safety of rhGH treatment. Bisulfite converted DNA of PB from 36 SGA born children treated long-term with rhGH and 18 SGA born children with no rhGH treatment (controls) were hybridized to the Illumina Infinium HumanMethylation 450k Bead Chip.

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Genome-wide profiling of PARP1 reveals an interplay with gene regulatory regions and DNA methylation

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