The Role of Zinc Finger Proteins During Target Gene Activation by HOM-C Proteins.

锌指蛋白在 HOM-C 蛋白激活靶基因过程中的作用。

• 批准号: 0090440
• 负责人: James Mahaffey
• 金额: $ 39万
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0090440&HistoricalAwards=false
• 关键词: Role; Zinc; Finger; Proteins; During

0090040MahaffeyHox genes encode homeodomain-containing transcription factors that specify body pattern during embryogenesis in all metazoans. In the fruit fly, Drosophila melanogaster these genes are located in the Antennapedia- and Bithorax-Complexes. Each individual hox gene is expressed in a specific anterior/posterior domain wherein the encoded protein specifies regional identity through activation of a specific set of target genes. However, the DNA binding properties of the different hox proteins are quite similar This has lead to the hypothesis that interactions with cofactors play an important role in target gene selection by the hox proteins, though few cofactors are known. Recent results from the Mahaffey lab indicate that regionally-expressed zinc finger transcription factors are likely cofactors for the Deformed (Dfd) and Sex combs reduced (Scr) hox proteins. Loss of the two, redundant zinc finger genes, disconnected (disco) and disco-related (disco-r) causes a phenotype similar to loss of Dfd and Scr. Dr. Mahaffey proposed that an interaction between the hox and zinc finger proteins supplies the additional specificity that is required for selection and activation of hox target genes. Further, he proposes that this may be a conserved mechanism that governs body plan specification in other regions of the embryo and in other animals. This hypothesis leads to several predictions that Dr. Mahaffey will test. Dr. Mahaffey will ectopically co-express Disco and Dfd in Drosophila to determine whether both proteins will cause a broader transformation than that of Dfd alone. He will investigate the possibility of molecular interactions between Disco and Dfd, including protein-protein and protein-DNA binding studies. He will also search for Disco/Disco-r response elements at known Dfd target genes, and, if found, he will undertake molecular characterizations of these response elements. To examine the possibility that this is a conserved mechanism, he will use RNAi to eliminate the disco/disco-r function(s) from beetle Tribolium to test whether this causes a homeotic transformation similar to that observed due to loss of Tc-Dfd and Tc-Scr.

0090040MahaffeyHox基因编码含有同源结构域的转录因子，这些转录因子在所有后生动物的胚胎发生过程中指定身体模式。在果蝇（Drosophila melanogaster）中，这些基因位于触角和双胸复合体中。每个hox基因在特定的前/后结构域表达，其中编码的蛋白质通过激活一组特定的靶基因来指定区域身份。然而，不同的hox蛋白的DNA结合特性非常相似，这导致了与辅助因子的相互作用在hox蛋白的靶基因选择中起重要作用的假设，尽管已知的辅助因子很少。Mahaffey实验室最近的研究结果表明，区域表达的锌指转录因子可能是畸形（Dfd）和性梳减少（Scr） hox蛋白的辅助因子。两个多余的锌指基因（断开的（disco）和与disco相关的（disco-r））的丢失会导致类似于Dfd和Scr丢失的表型。Mahaffey博士提出，hox和锌指蛋白之间的相互作用为hox靶基因的选择和激活提供了额外的特异性。此外，他提出，这可能是一种保守的机制，在胚胎的其他区域和其他动物中控制着身体计划规范。这一假设引出了马哈菲博士将要验证的几个预测。Mahaffey博士将在果蝇中异位共表达Disco和Dfd，以确定这两种蛋白质是否会比单独表达Dfd引起更广泛的转化。他将研究Disco和Dfd之间分子相互作用的可能性，包括蛋白质-蛋白质和蛋白质- dna结合研究。他还将在已知的Dfd靶基因中寻找Disco/Disco-r反应元件，如果找到，他将对这些反应元件进行分子表征。为了检验这是一种保守机制的可能性，他将使用RNAi来消除甲虫Tribolium中的disco/disco-r功能，以测试这是否会导致类似于由于Tc-Dfd和Tc-Scr丢失而观察到的同质转化。