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

• DOI: 10.1038/s41467-018-03856-y
• Publication Date: 2018-04-04T14:29:47Z
• Authors: Jie Wang; Cristina Zibetti; Peng Shang; Srinivasa R. Srip...; Pingwu Zhang; Marisol Cano; Thanh Hoang; Shuli Xia; Hongkai Ji; Shannath L. Merbs; Donald J. Zack; James T. Handa; Debasish Sinha; Seth Blackshaw; Jiang Qian
• Keywords: 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

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