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Jiang Qian, Verity Frances Oliver, Jun Wan, Shannath L Merbs; Genome-wide DNA methylation changes associated with retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1275.
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The retinal degeneration 1 (rd1) mouse is a well-studied animal model of retinitis pigmentosa. These mice undergo an apoptotic-like photoreceptor loss beginning at postnatal day 10 (P10) and peaking at P14. By P35, essentially all rods and most cones are lost. Despite many studies of programmed cell death in models of retinal degeneration, little is known about epigenetic changes that occur before, during and after cell death.
To analyze the genome-wide DNA methylation changes that occur during retinal degeneration, retinal DNA from P10, P14 and P35 rd1 mice was enriched for methylated DNA and compared on the CHARM array to wild type retinal DNA at the same time points.
1,916, 1,477 and 2,905 differentially methylated regions (DMRs) were identified at P10, P14 and P35, respectively. Methylation of many of these DMRs showed negative correlation with gene expression in the rd1 mouse, suggesting a possible functional consequence of the methylation changes. Gene ontology analysis revealed that DMR-containing genes were enriched for genes involved in metabolic pathways. The most significant differentially methylated region was in the gene phosphatidylcholine 2-Acylhydrolase 2E (Pla2g2e), which is known to be involved in such diverse biological functions as inflammation, cell growth, signaling and death. Differential methylation of Pla2g2e was confirmed by bisulfite pyrosequencing.
Our study provides a genome-wide survey of the DNA methylation changes that occur during retinal degeneration in the rd1 mouse. Because environmental factors can contribute to the pathogenesis of retinal degeneration, a better understanding of the epigenetic changes that facilitate interaction between environmental and genetic factors that can lead to disease should ultimately help in the design of novel therapeutic approaches.
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