共激活蛋白在视网膜感光细胞发育中的分子调控机制

项目名称： 共激活蛋白在视网膜感光细胞发育中的分子调控机制

项目编号： No.31271400

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 彭广华

作者单位： 中国人民解放军总医院

项目金额： 80万元

中文摘要： 视网膜感光受体基因的精确转录和调控对感光细胞的发育和存活起着至关重要的作用，这种调控作用是通过一系列转录因子与其靶基因相互作用来完成的。在复杂的调控过程中，最重要的转录因子是视锥-视杆同源异形框 (cone-rod homeobox, Crx)，它调控视网膜感光受体基因的表达，Crx基因突变可引起多种人类视网膜变性疾病。我们的前期工作已鉴别出一系列Crx相关性蛋白，其中包括三种共激活蛋白：Gcn5、Cbp 和 p300，此类蛋白与染色体塑形有着密切的关系。我们近期的研究结果提示这些共激活蛋白是视网膜感光受体基因Crx调控通路上的重要成份。本研究的中心假设是：Crx与其共激活蛋白的协同作用通过改变染色体的构型，在视网膜感光细胞发育和存活过程中调控感光受体基因的表达。通过该研究确立哺乳类动物视网膜感光细胞特异性基因的分子调控机制，为寻找视网膜感光细胞变性的病因治疗提供理论根据。

中文关键词： 视网膜；感光细胞；基因调控；共激活蛋白；视锥-视杆同源异形框

英文摘要： Precise transcription and regulation of photoreceptor gene in retinal is playing an important role for the development and maintenance of photoreceptor cell through interactions between transcription factors and their target gene. cone-rod homeobox(Crx) is the most important transcription factor required for gene express of both cone and rod photoreceptors during the complex regulation process, and Crx mutations could cause several forms of retinal degeneration. Our previous research have found a series of Crx-related protein, including three co-activator proteins: Gcn5、Cbp and p300, all of which belong to histone acetyltransferases(HATs) and have a close relationship with chromosome remodeling. Our recent research results suggest that these co-activator proteins are important components in the retinal photoreceptor gene Crx regulatory pathway. The central hypothesis of this research is that Crx regulate the express of photoreceptor gene cooperatively with those co-activator proteins by altering the chromosomal organization. We will verify this hypothesis in this research and determine the molecular mechanism of regulating mammalian retina photoreceptor cell-specific gene, to provide a theoretical basis to the etiological treatment for retinal photoreceptor cell degeneration.

英文关键词： retina；photoreceptor；gene regulation；co-activator protein；cone-rod homeobox