Early cis-regulatory events in the formation of retinal horizontal cells.

Early cis-regulatory events in the formation of retinal horizontal cells.
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DOI:
10.1016/j.ydbio.2021.03.016
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发表时间:
2021-08
影响因子:
2.7
通讯作者:
Emerson MM
Emerson MM
中科院分区:
生物学3区
文献类型:
--
作者:
Schick E;Gonzalez KC;Dutta P;Hossain K;Ghinia Tegla MG;Emerson MM

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在视网膜发育过程中,多能和限制性祖细胞产生视网膜的所有神经元细胞。其中包括水平细胞,它们是调节来自光感受器的光诱导信号的中间神经元。本研究利用新的顺式调控元件的鉴定作为一种方法来检查基因调控网络,指导水平细胞的发展。在这里,我们描述了顺式调控元件,或增强子,水平细胞相关基因PTF1A,ONECUT1(OC 1),TFAP 2A(AP 2A),和LHX 1的屏幕。OC1ECR 22和Tfap 2aACR 5元件分别显示为OC1和TFAP 2A的潜在增强子,并且在发育水平细胞中具有特异性活性。OC1ECR 22元件被PTF1A和RBPJ激活,这转化为OC1表达的调节,并表明PTF1A是发育水平细胞中OC1表达的直接激活剂。Tfap2aACR 5元件内负责其激活的区域被确定为命名为基序4的100 bp序列。OC1ECR22和Tfap2aACR5都受到核受体THRB和RXRG的负调控,OC1和AP2A的表达也是如此,这表明核受体可能在水平细胞发育的负调控中起作用。
During retinal development, multipotent and restricted progenitor cells generate all of the neuronal cells of the retina. Among these are horizontal cells, which are interneurons that modulate the light-induced signal from photoreceptors. This study utilizes the identification of novel cis-regulatory elements as a method to examine the gene regulatory networks that direct the development of horizontal cells. Here we describe a screen for cis-regulatory elements, or enhancers, for the horizontal cell-associated genes PTF1A, ONECUT1 (OC1), TFAP2A (AP2A), and LHX1. The OC1ECR22 and Tfap2aACR5 elements were shown to be potential enhancers for OC1 and TFAP2A, respectively, and to be specifically active in developing horizontal cells. The OC1ECR22 element is activated by PTF1A and RBPJ, which translates to regulation of OC1 expression and suggests that PTF1A is a direct activator of OC1 expression in developing horizontal cells. The region within the Tfap2aACR5 element that is responsible for its activation was determined to be a 100 bp sequence named Motif 4. Both OC1ECR22 and Tfap2aACR5 are negatively regulated by the nuclear receptors THRB and RXRG, as is the expression of OC1 and AP2A, suggesting that nuclear receptors may have a role in the negative regulation of horizontal cell development.
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