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Jiang Qian, Jun Wan, Verity Oliver, Donald Zack, Shannath Merbs; Correlating Whole Genome DNA Methylation Patterns with Retinal Expression and Alternative Splicing. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2615. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
DNA methylation is a major epigenetic modification that plays an important role in multiple cellular processes. It is generally believed that DNA methylation inhibits gene expression. However, how exactly the DNA methylation regulates tissue-specific gene expression and splicing remains unclear. In this study, we performed genome-wide DNA methylation profiling in retina and brain to evaluate the correlation between DNA methylation and tissue-specific gene regulation.
DNA methylation profiling on two adult mouse tissues, retina and brain, was conducted using the comprehensive high-throughput array for relative methylation (CHARM) NimbleGen tiling array. Affymetrix exon microarrays were also used to measure the gene expression and splicing differences between retina and brain. Bioinformatics methods were developed and employed to analyze the data and correlate the DNA methylation, gene expression and splicing.
Numerous tissue-specific differentially methylated regions (tDMRs) were identified. These tDMRs located in various genomic regions, including promoter, exon, intron and intergenic regions. They were enriched in CpG island shores, but depleted in CpG islands. We then integrated these tDMRs with the transcriptome data measured in the corresponding tissues by exon microarray. DMRs that negatively correlated with downstream gene expression tended to be close to transcription start sites. Tissue-specific genes were more likely to be regulated by differential methylation than expected. A large number of DMRs located in exons or introns correlated with the expression of an adjacent exon, suggesting a potential role of DNA methylation in tissue-specific splicing.
Our work provides a large-scale survey of differential DNA methylation of retina-specific genes and lays the foundation for further mechanistic studies of the biological role of DNA methylation in tissue-specific gene regulation.
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