Cell-specific DNA methylation patterns of retina-specific genes.
Cell-specific DNA methylation patterns of retina-specific genes.
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DOI：
10.1371/journal.pone.0032602
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zack DJ
中科院分区：
文献类型：
--
作者：
Merbs SL;Khan MA;Hackler L Jr;Oliver VF;Wan J;Qian J;Zack DJ
许多研究表明，表观遗传机制在胚胎发生、配子体发生和其他形式的组织特异性基因调控过程中对基因表达的调控起着重要作用。我们试图探索表观遗传学，特别是DNA甲基化，在视网膜细胞类型限制性基因表达的建立和维持中的可能作用。为了评估DNA甲基化状态与视网膜基因表达水平的关系，我们对WERI和Y79人视网膜母细胞瘤细胞系中具有代表性的杆状和锥状光感受器特异性基因转录起始位点（TSS）周围1000 bp区域进行亚硫酸盐序列分析和基因表达分析。接下来，对小鼠视网膜和非表达组织中的同源基因进行亚硫酸盐测序。最后，对激光捕获显微解剖分离的光感受器和非光感受器视网膜细胞进行亚硫酸盐测序。视网膜母细胞瘤细胞系中视紫红质（RHO）、视网膜结合蛋白3 （RBP3， IRBP）视锥蛋白短波敏感（OPN1SW）、视锥蛋白中波敏感（OPN1MW）和视锥蛋白长波敏感（OPN1LW）的差异甲基化与基因表达水平呈负相关。同样，与非表达组织相比，我们发现小鼠视网膜中Rho和Rbp3启动子区域的组织特异性低甲基化，并且还观察到视网膜表达的microrna的低甲基化。Rho和Rbp3启动子区域在表达光感受器细胞中未甲基化，而在来自内核层的非表达的非光感受器细胞中甲基化。光感受器特异性基因的第三种区域低甲基化模式在非表达光感受器亚群中被发现（Rho在Nrl−/−小鼠的锥细胞中，Opn1sw在杆状细胞中）。这些结果表明，许多光感受器特异性基因具有细胞特异性差异DNA甲基化，其表达水平呈负相关。此外，这些细胞特异性模式表明，DNA甲基化可能在哺乳动物视网膜发育过程中调节光感受器基因表达中发挥重要作用。
Many studies have demonstrated that epigenetic mechanisms are important in the regulation of gene expression during embryogenesis, gametogenesis, and other forms of tissue-specific gene regulation. We sought to explore the possible role of epigenetics, specifically DNA methylation, in the establishment and maintenance of cell type-restricted gene expression in the retina. To assess the relationship between DNA methylation status and expression level of retinal genes, bisulfite sequence analysis of the 1000 bp region around the transcription start sites (TSS) of representative rod and cone photoreceptor-specific genes and gene expression analysis were performed in the WERI and Y79 human retinoblastoma cell lines. Next, the homologous genes in mouse were bisulfite sequenced in the retina and in non-expressing tissues. Finally, bisulfite sequencing was performed on isolated photoreceptor and non-photoreceptor retinal cells isolated by laser capture microdissection. Differential methylation of rhodopsin (RHO), retinal binding protein 3 (RBP3, IRBP) cone opsin, short-wave-sensitive (OPN1SW), cone opsin, middle-wave-sensitive (OPN1MW), and cone opsin, long-wave-sensitive (OPN1LW) was found in the retinoblastoma cell lines that inversely correlated with gene expression levels. Similarly, we found tissue-specific hypomethylation of the promoter region of Rho and Rbp3 in mouse retina as compared to non-expressing tissues, and also observed hypomethylation of retinal-expressed microRNAs. The Rho and Rbp3 promoter regions were unmethylated in expressing photoreceptor cells and methylated in non-expressing, non-photoreceptor cells from the inner nuclear layer. A third regional hypomethylation pattern of photoreceptor-specific genes was seen in a subpopulation of non-expressing photoreceptors (Rho in cones from the Nrl −/− mouse and Opn1sw in rods). These results demonstrate that a number of photoreceptor-specific genes have cell-specific differential DNA methylation that correlates inversely with their expression level. Furthermore, these cell-specific patterns suggest that DNA methylation may play an important role in modulating photoreceptor gene expression in the developing mammalian retina.
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影响因子：
30.8
作者：
Mears, AJ;Kondo, M;Swaroop, A
通讯作者：
Swaroop, A
影响因子：
4.4
作者：
Karali, Marianthi;Peluso, Ivana;Banfi, Sandro
通讯作者：
Banfi, Sandro
影响因子：
2.9
作者：
Boatright, JH;Nickerson, JM;Borst, DE
通讯作者：
Borst, DE
影响因子：
2
作者：
Borst, DE;Boatright, JH;Nickerson, JM
通讯作者：
Nickerson, JM
影响因子：
2.9
作者：
Deeb, S. S.;Bisset, D.;Fu, L.
通讯作者：
Fu, L.