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Samuel Shaomin Zhang, Chen Yang, Jing Lu, Evgenya Popova, Colin J Barnstable; Epigenetic analysis of transcriptional accessibility of immune-related genes during retina maturation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5001.
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Many retinal diseases, such as AMD, glaucoma, and diabetic retinopathy, may be caused by excessive or abnormal inflammatory responses. The physiological functions of extracellular and intracellular signaling molecules of immune responses have been well characterized and the genes related to those immune responses are largely identified. The histone H3K4 dimethylation (H3K4me2) and H3K27 trimethylation (H3K27me3) are markers associated with gene promoter regions and represent the gene’s transcriptional accessibility positive or negative respectively. They have, however, not been elucidated in the genes related to those immune responses of retina. In this study, we explored the transcriptional accessibility of genes related to immune or inflammatory responses during retina maturation.
ChIP-Seq database were collected from our previous GEO data repository (GSE38500) and ENCODE/LICR database. All data were visualized in UCSC Genome Browser (www.genome.ucsc.edu) for epigenetic mapping. Hierarchical cluster analysis was performed through Gene Cluster 3.0 (Eisen Lab). About 25K genes were pre-categorized by their functions from RefSeq database (NCBI). Then genes of each categorized group were classified into two clusters through average linkage depending on their H3K4me2 and H3K27me3 accumulation. Tree analysis was done via Java Tree View (version 1.1.6r2) for visualization.
In this study, we focused on interleukin/ interleukin receptors, complement and genes in the toll-like receptor family, and major signaling pathways such as, PI3K, NFkB, and STATs. Among these genes, interleukin receptor related genes and intracellular signaling molecules exhibit higher transcriptional accessibility compared to their ligands. Epigenetic mapping of the toll-like receptor family revealed that 3 out of 13 TLRs exhibit H3K4me2 accumulation during retina development, suggesting that TLR2, TLR3, and TLR9 are potentially transcriptional accessible in the retina. We also found that the most of the NFkB signaling molecules exhibited transcriptional accessibility, implying their essential roles in inflammatory regulation during retina maturation.
During development, many immune response genes in the retina are transcriptionally accessible. The majority of these genes are interleukin receptors and intracellular signaling genes in the PI3K, NFkB, and STAT pathways.
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