Deletion of a remote enhancer near ATOH7 disrupts retinal neurogenesis, causing NCRNA disease.
Deletion of a remote enhancer near ATOH7 disrupts retinal neurogenesis, causing NCRNA disease.
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DOI：
10.1038/nn.2798
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发表时间：
2011-05
影响因子：
25
通讯作者：
Glaser, Tom
中科院分区：
文献类型：
--
作者：
Ghiasvand, Noor M.;Rudolph, Dellaney D.;Mashayekhi, Mohammad;Brzezinski, Joseph A.;Goldman, Daniel;Glaser, Tom
患有非综合征性先天性视网膜不附着（NCRNA）的个体从出生起就完全失明。生活在伊朗北呼罗珊邻近村庄的约1%的库尔德人患有这种疾病。我们发现NCRNA是由6523bp的缺失引起的，该缺失跨越了ATOH7 （Math5）上游20 kb的远端顺式调控元件，ATOH7是视网膜神经节细胞（RGC）和视神经发育所需的bHLH转录因子基因。在人类中，RGCs的缺失会刺激玻璃体内胎儿血管的大量新生血管生长，并导致早期视网膜脱离。远端ATOH7元件似乎作为次级或“影子”转录增强子。它与初级增强子的序列相似性最小，初级增强子与Atoh7启动子接近，但在小鼠视网膜中以相同的时空模式驱动转基因表达。人类转基因也在斑马鱼中起作用，反映了深刻的进化保护。当视网膜神经发生时，这些双增强因子可能在眼睛发育的早期关键阶段增强Atoh7的表达。
Individuals with nonsyndromic congenital retinal nonattachment (NCRNA) are totally blind from birth. The disease afflicts ~1% of Kurdish people living in a group of neighboring villages in North Khorasan, Iran. We show NCRNA is caused by a 6523bp deletion that spans a remote cis regulatory element 20 kb upstream from ATOH7 (Math5), a bHLH transcription factor gene required for retinal ganglion cell (RGC) and optic nerve development. In humans, the absence of RGCs stimulates massive neovascular growth of fetal blood vessels within the vitreous, and early retinal detachment. The remote ATOH7 element appears to act as a secondary or ‘shadow’ transcriptional enhancer. It has minimal sequence similarity to the primary enhancer, which is close to the Atoh7 promoter, but drives transgene expression with an identical spatiotemporal pattern in the mouse retina. The human transgene also functions in zebrafish, reflecting deep evolutionary conservation. These dual enhancers may reinforce Atoh7 expression during early critical stages of eye development when retinal neurogenesis is initiated.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
2.7
作者：
Hufnagel RB;Le TT;Riesenberg AL;Brown NL
通讯作者：
Brown NL
影响因子：
9.8
作者：
Chen, Jing;Smith, Lois E. H.
通讯作者：
Smith, Lois E. H.
影响因子：
4.1
作者：
BRODRICK, JD
通讯作者：
BRODRICK, JD
DOI：
10.1007/978-0-387-69069-8_8
发表时间：
2010-01-01
期刊：
PEDIATRIC NEURO-OPHTHALMOLOGY, SECOND EDITION
影响因子：
--
作者：
Brodsky, Michael C.
通讯作者：
Brodsky, Michael C.