ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration

Male Nicotiana Science Primary Cell Culture 610 Retinal Pigment Epithelium Complex Mixtures Article Histone Deacetylases Epigenesis, Genetic Macular Degeneration 03 medical and health sciences Smoke Humans Eye Proteins Aged Aged, 80 and over 0303 health sciences Q High-Throughput Nucleotide Sequencing Epithelial Cells Chromatin Case-Control Studies Female Genome-Wide Association Study Transcription Factors
DOI: 10.1038/s41467-018-03856-y Publication Date: 2018-04-04T14:29:47Z
ABSTRACT
Age-related macular degeneration (AMD) is a significant cause of vision loss in the elderly. The extent to which epigenetic changes regulate AMD progression unclear. Here we globally profile chromatin accessibility using ATAC-Seq retina and retinal pigmented epithelium (RPE) from control patients. Global decreases occur RPE with early AMD, advanced disease, suggesting that dysfunction drives disease onset. Footprints photoreceptor RPE-specific transcription factors are enriched differentially accessible regions (DARs). Genes associated DARs show altered expression AMD. Cigarette smoke treatment cells recapitulates seen providing an link between known risk factor for pathology. Finally, overexpression HDAC11 partially responsible observed reduction accessibility, may be potential new therapeutic target
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