ATAC-Seq 分析揭示了年龄相关性黄斑变性中染色质可及性的广泛降低。
ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration.
机构信息
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
出版信息
Nat Commun. 2018 Apr 10;9(1):1364. doi: 10.1038/s41467-018-03856-y.
Age-related macular degeneration (AMD) is a significant cause of vision loss in the elderly. The extent to which epigenetic changes regulate AMD progression is unclear. Here we globally profile chromatin accessibility using ATAC-Seq in the retina and retinal pigmented epithelium (RPE) from AMD and control patients. Global decreases in chromatin accessibility occur in the RPE with early AMD, and in the retina of advanced disease, suggesting that dysfunction in the RPE drives disease onset. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs). Genes associated with DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells recapitulates chromatin accessibility changes seen in AMD, providing an epigenetic link between a known risk factor for AMD and AMD pathology. Finally, overexpression of HDAC11 is partially responsible for the observed reduction in chromatin accessibility, suggesting that HDAC11 may be a potential new therapeutic target for AMD.
年龄相关性黄斑变性（AMD）是老年人视力丧失的一个重要原因。表观遗传变化在多大程度上调节 AMD 的进展尚不清楚。在这里，我们使用 ATAC-Seq 在 AMD 和对照患者的视网膜和视网膜色素上皮（RPE）中进行了全基因组染色质可及性分析。早期 AMD 时 RPE 中的染色质可及性全局降低，晚期疾病时视网膜中的染色质可及性全局降低，表明 RPE 功能障碍导致疾病发生。光感受器和 RPE 特异性转录因子的足迹在差异可及区域（DAR）中富集。与 DAR 相关的基因在 AMD 中表达改变。RPE 细胞的香烟烟雾处理再现了 AMD 中观察到的染色质可及性变化，为 AMD 的一个已知危险因素和 AMD 病理学之间提供了一个表观遗传联系。最后，HDAC11 的过表达部分导致观察到的染色质可及性降低，表明 HDAC11 可能是 AMD 的一个潜在新的治疗靶点。
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