Epigenomic landscapes of retinal rods and cones.
Epigenomic landscapes of retinal rods and cones.
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视网膜视杆细胞和视锥细胞的表观基因组图谱
DOI：
10.7554/elife.11613
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发表时间：
2016-03-07
期刊：
影响因子：
7.7
通讯作者：
Nathans J
中科院分区：
文献类型：
--
作者：
Mo A;Luo C;Davis FP;Mukamel EA;Henry GL;Nery JR;Urich MA;Picard S;Lister R;Eddy SR;Beer MA;Ecker JR;Nathans J
视杆和视锥光感受器在许多方面高度相似，但它们具有重要的功能和分子差异。在这里，我们研究了小鼠视杆细胞和视锥细胞中DNA甲基化和染色质可及性的全基因组模式，并将这些特征与基因表达、组蛋白标记、转录因子结合和DNA序列基序的差异相关联。视杆细胞中NR 2 E3的缺失使其表观基因组转变为更像视锥细胞的状态。这些数据进一步揭示了视网膜光感受器和脑神经元之间DNA甲基化的广泛差异。令人惊讶的是，我们也发现了相当大一部分的DNA低甲基化区域在成人杆，是不是在活跃的染色质。这些区域中的许多区域表现出在神经元发育早期活跃的调控区域的特征，这表明这些区域可能由于成熟杆中高度致密的染色质而保持甲基化不足。这项工作定义了视杆细胞和视锥细胞的表观基因组景观，揭示了与感光细胞发育和功能相关的特征。http://dx.doi.org/10.7554/eLife.11613.001人类的视觉是由眼睛后部的一层感光细胞构成的，称为视网膜。视网膜的表面是由专门的感觉细胞，称为杆和锥。视杆细胞检测非常微弱的光，而视锥细胞对光不太敏感，但用于检测颜色。视杆细胞和视锥细胞一起收集创建图像所需的信息，然后将图像传输到大脑。几十年来，人们一直在研究视杆细胞和视锥细胞，遗传分析揭示了导致细胞发育成视杆细胞或视锥细胞的基因表达模式。研究人员还确定了控制这些模式的几个关键调控基因，但对控制基因表达的其他因素的作用知之甚少。对DNA的化学修饰或对与DNA相关的蛋白质的修饰-统称为表观遗传修饰-可以促进或抑制附近基因的激活。现在，Mo等人已经表明，小鼠的视杆细胞和视锥细胞具有非常不同的表观遗传修饰模式。实验还表明，许多被标记为促进基因激活的DNA片段含有已知的视杆细胞特异性或视锥细胞特异性基因;视杆细胞需要一个已知的调控基因来发展其特定的表观遗传修饰模式。最后，Mo等人表明，脑细胞与视杆细胞和视锥细胞之间的表观遗传调控不同。这些对视杆细胞和视锥细胞基因的表观遗传调控的见解可能有助于解释为什么一些患有由相同基因突变引起的眼病的人可能在不同年龄出现症状或以不同的速度失去视力。关于基因调控的新信息也可能帮助科学家重新编程干细胞，使其成为健康的视杆细胞或视锥细胞，这些细胞可以移植到患有眼疾的人身上，以恢复他们的视力。DOI：http://dx.doi.org/10.7554/eLife.11613.002网站
Rod and cone photoreceptors are highly similar in many respects but they have important functional and molecular differences. Here, we investigate genome-wide patterns of DNA methylation and chromatin accessibility in mouse rods and cones and correlate differences in these features with gene expression, histone marks, transcription factor binding, and DNA sequence motifs. Loss of NR2E3 in rods shifts their epigenomes to a more cone-like state. The data further reveal wide differences in DNA methylation between retinal photoreceptors and brain neurons. Surprisingly, we also find a substantial fraction of DNA hypo-methylated regions in adult rods that are not in active chromatin. Many of these regions exhibit hallmarks of regulatory regions that were active earlier in neuronal development, suggesting that these regions could remain undermethylated due to the highly compact chromatin in mature rods. This work defines the epigenomic landscapes of rods and cones, revealing features relevant to photoreceptor development and function. DOI: http://dx.doi.org/10.7554/eLife.11613.001 Vision in humans is made possible by a light-sensing sheet of cells at the back of the eye called the retina. The surface of the retina is populated by specialized sensory cells, known as rods and cones. The rod cells detect very dim light, while the cones are less sensitive to light but are used to detect color. Together, the rods and cones gather the information needed to create a picture that is then transmitted to the brain. Rods and cones have been studied for decades, and genetic analyses have revealed the patterns of gene expression that lead a cell to develop into either a rod or a cone. Researchers have also identified several key regulatory genes that control these patterns, but less is known about the role of other factors that control the expression of genes. Chemical modifications to DNA or modifications to the proteins associated with DNA – which are collectively called epigenetic modifications – can either promote or inhibit the activation of nearby genes. Now, Mo et al. have shown that rods and cones from mice have very different patterns of epigenetic modifications. The experiments also revealed that many sections of DNA that are marked to promote gene activation contain known rod-specific or cone-specific genes; and that rod cells need a known regulatory gene to develop their specific pattern of epigenetic modifications. Finally, Mo et al. showed that epigenetic regulation differed between brain cells and rods and cones. These insights into epigenetic regulation of rod and cone genes may help explain why some people with eye diseases caused by the same genetic mutation may develop symptoms at different ages or lose vision at different rates. The new information about gene regulation may also help scientists to reprogram stem cells to become healthy rods or cones that could be transplanted into people with eye disease to restore their vision. DOI: http://dx.doi.org/10.7554/eLife.11613.002