ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration.
ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration.
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DOI：
10.1038/s41467-018-03856-y
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发表时间：
2018-04-10
影响因子：
16.6
通讯作者：
Qian J
中科院分区：
文献类型：
--
作者：
Wang J;Zibetti C;Shang P;Sripathi SR;Zhang P;Cano M;Hoang T;Xia S;Ji H;Merbs SL;Zack DJ;Handa JT;Sinha D;Blackshaw S;Qian J
老年性黄斑变性(AMD)是老年人视力丧失的重要原因。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对AMD和对照组患者的视网膜和视网膜色素上皮(RPE)中染色质的可及性进行全球分析。染色质可及性在早期AMD的RPE和晚期疾病的视网膜中出现全球性的下降，这表明RPE的功能障碍导致了疾病的发生。光感受器和RPE特异性转录因子的足迹在差异可及区(DAR)中丰富。与DARS相关的基因在AMD中的表达发生了变化。香烟烟雾对RPE细胞的治疗概括了在AMD中看到的染色质可及性变化，在AMD的已知危险因素和AMD病理之间提供了表观遗传学联系。最后，HDAC11的过度表达是染色质可及性减少的部分原因，这表明HDAC11可能是AMD潜在的新治疗靶点。老年性黄斑变性(AMD)导致视网膜色素上皮(RPE)功能障碍和视力丧失。在这里，作者进行atac-seq来研究染色质的可及性，并发现在AMD中，差异可及区富含光感受器和RPE特异性转录因子。
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. Age-related macular degeneration (AMD) leads to dysfunctional retinal pigment epithelium (RPE) and vision loss. Here, the authors perform ATAC-seq to study chromatin accessibility and find that differentially accessible regions are enriched for photoreceptor and RPE-specific transcription factors in AMD
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
4.5
作者：
Hao H;Kim DS;Klocke B;Johnson KR;Cui K;Gotoh N;Zang C;Gregorski J;Gieser L;Peng W;Fann Y;Seifert M;Zhao K;Swaroop A
通讯作者：
Swaroop A
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1124/jpet.107.120188
发表时间：
2007-06-01
影响因子：
3.5
作者：
Kim, Hyeon Ju;Rowe, Michael;Chuang, De-Maw
通讯作者：
Chuang, De-Maw