DNA demethylation is a driver for chick retina regeneration.
DNA demethylation is a driver for chick retina regeneration.
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DOI：
10.1080/15592294.2020.1747742
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发表时间：
2020-09
期刊：
影响因子：
3.7
通讯作者：
Del Rio-Tsonis K
中科院分区：
文献类型：
--
作者：
Luz-Madrigal A;Grajales-Esquivel E;Tangeman J;Kosse S;Liu L;Wang K;Fausey A;Liang C;Tsonis PA;Del Rio-Tsonis K
细胞重编程重置表观遗传格局，以驱动转录程序和细胞身份的转变。胚胎雏鸡在视网膜切除后，可以在FGF2存在的情况下，通过视网膜色素上皮(RPE)的重新编程再生完整的神经视网膜。在本研究中，我们系统地分析了鸡视网膜色素上皮损伤前和重编程不同阶段的再编程能力。除了在RPE重编程过程中与表观遗传修饰相关的基因表达的变化外，我们还观察到与二价染色质相关的组蛋白标记(H3K27me3/H3K4me3)以及DNA去甲基化过程的中间产物包括5hmC和5caC的动态变化。通过全基因组亚硫酸盐测序(WGBS)对甲基组的综合分析证实了DNA甲基化模式的广泛重排，包括在与染色质组织和成纤维细胞生长因子产生相关的基因的启动子上发现的差异甲基化区域(DMRS)。我们还发现TET甲基胞嘧啶双加氧酶3(TET3)是DNA去甲基化和视网膜再生的重要因子，能够在没有外源FGF2的情况下重新编程RPE。总之，我们证明了RPE重编程早期的损伤会触发全基因组染色质的动态变化，包括二价染色质和DNA甲基化。在FGF2存在的情况下，这些动态修饰在形成新视网膜的承诺中得到进一步维持。我们的发现表明，活跃的DNA去甲基化是一个重要的过程，可以用来消除表观遗传障碍，以便在哺乳动物中再生视网膜。碱基对；DMR：差异甲基化区域；DMC：差异甲基化胞嘧啶；GFP：绿色荧光蛋白；PCR：聚合酶链式反应。Tet：10-11易位；RPE：视网膜色素上皮。
Cellular reprogramming resets the epigenetic landscape to drive shifts in transcriptional programmes and cell identity. The embryonic chick can regenerate a complete neural retina, after retinectomy, via retinal pigment epithelium (RPE) reprogramming in the presence of FGF2. In this study, we systematically analysed the reprogramming competent chick RPE prior to injury, and during different stages of reprogramming. In addition to changes in the expression of genes associated with epigenetic modifications during RPE reprogramming, we observed dynamic changes in histone marks associated with bivalent chromatin (H3K27me3/H3K4me3) and intermediates of the process of DNA demethylation including 5hmC and 5caC. Comprehensive analysis of the methylome by whole-genome bisulphite sequencing (WGBS) confirmed extensive rearrangements of DNA methylation patterns including differentially methylated regions (DMRs) found at promoters of genes associated with chromatin organization and fibroblast growth factor production. We also identified Tet methylcytosine dioxygenase 3 (TET3) as an important factor for DNA demethylation and retina regeneration, capable of reprogramming RPE in the absence of exogenous FGF2. In conclusion, we demonstrate that injury early in RPE reprogramming triggers genome-wide dynamic changes in chromatin, including bivalent chromatin and DNA methylation. In the presence of FGF2, these dynamic modifications are further sustained in the commitment to form a new retina. Our findings reveal active DNA demethylation as an important process that may be applied to remove the epigenetic barriers in order to regenerate retina in mammals. bp: Base pair; DMR: Differentially methylated region; DMC: Differentially methylated cytosines; GFP: Green fluorescent protein; PCR: Polymerase chain reaction. TET: Ten-eleven translocation; RPE: retinal pigment epithelium.
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抑制 H3K27me3 组蛋白去甲基化酶活性可阻止斑马鱼侧线神经丘的增殖再生
影响因子：
4.8
作者：
Bao B;He Y;Tang D;Li W;Li H
通讯作者：
Li H
在发育，重编程和肿瘤发生过程中，视网膜的动态表观遗传景观。
影响因子：
16.2
作者：
Aldiri I;Xu B;Wang L;Chen X;Hiler D;Griffiths L;Valentine M;Shirinifard A;Thiagarajan S;Sablauer A;Barabas ME;Zhang J;Johnson D;Frase S;Zhou X;Easton J;Zhang J;Mardis ER;Wilson RK;Downing JR;Dyer MA;St. Jude Children’s Research Hospital—Washington University Pediatric Cancer Genome Project
通讯作者：
St. Jude Children’s Research Hospital—Washington University Pediatric Cancer Genome Project
DOI：
10.1038/nrg3473
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Burns ME;Stevens B
通讯作者：
Stevens B
影响因子：
12.3
作者：
Akalin A;Kormaksson M;Li S;Garrett-Bakelman FE;Figueroa ME;Melnick A;Mason CE
通讯作者：
Mason CE