RUI - Functional Characterization of a Nematode Gene Related to the Class II bHLH Protein, ABF-1

碱性螺旋-环-螺旋蛋白是从无脊椎动物到脊椎动物等生物中细胞增殖和分化的重要转录调节因子。最近，从线虫线虫中克隆了一个与哺乳动物碱性螺旋-环-螺旋蛋白激活的B细胞因子1(ABF-1)密切相关的新基因，命名为CeABF-1。本研究的目的包括1)研究CeABF-1基因的功能；2)阐明CeABF-1蛋白的转录特性；3)确定CeABF-1调控的靶基因(S)。为了实现这些特定的目标，将进行基因功能和表达研究，以描述CeABF-1在线虫中的作用。功能研究将整合广泛的遗传和生化技术，包括RNA微量注射和用于表达分析的转基因动物的开发。通过基因转染、凝胶迁移率改变分析和基因显微分析，分析CeABF-1基因的转录特性和调控靶基因(S)。该项目将允许比较线虫和人类的HLH基因功能，并确定对细胞过程重要的保守分子途径。这些研究结果将有助于阐明该线虫与人类ABF-1蛋白的进化和生物学关系。在从无脊椎动物到脊椎动物的各种生物中，螺旋-环-螺旋(Helix-loop-Helix，HLH)蛋白是细胞增殖和分化的重要转录调节因子。促黄体生成素蛋白作为免疫系统功能和肌肉发育的强大中介的重要性已经得到了很好的证实。这些研究的意义将有助于确定线虫HLH基因的生物学功能，命名为CeABF-1，并将为阐明控制细胞限制性真核基因表达的分子机制提供数据。本项目将加深对受CeABF-1蛋白控制的靶基因(S)的了解，并了解虫子CeABF-1与人类同源激活的B细胞因子1(ABF-1)之间的祖先关系。

Basic helix-loop-helix proteins are important transcriptional regulators of cellular proliferation and differentiation in organisms ranging from invertebrates to vertebrates. Recently, a new gene closely related to the mammalian basic helix-loop-helix protein activated B-cell factor 1 (ABF-1), designated CeABF-1, was cloned from the nematode Caenorhabditis elegans. The objectives of the research include 1) investigating the function of the CeABF-1 gene; 2) elucidating the transcriptional properties of the CeABF-1 protein; 3) identifying the target gene(s) regulated by CeABF-1. To accomplish these specific goals, gene function and expression studies will be performed to delineate the role of CeABF-1 in the nematode. The functional studies will integrate a broad spectrum of genetic and biochemical techniques, including RNA microinjections and the development of transgenic animals for expression analyses. The transcriptional properties and target gene(s) regulated by CeABF-1 will be analyzed using DNA transfections, electrophoretic-mobility shift assays and DNA microanalysis. This project will allow for the comparison of HLH gene function in both nematodes and humans and identify conserved molecular pathways important for cellular processes. The results of these studies will help to elucidate the evolutionary as well as the biological relationship between the nematode and human ABF-1 protein. Helix-loop-helix (HLH) proteins are important transcriptional regulators of cellular proliferation and differentiation in organisms ranging from invertebrates to vertebrates. The importance of HLH proteins as potent mediators of immune system function and muscle development has been well established. The significance of these studies will allow for the determination of the biological function of the nematode Caenorhabditis elegans HLH gene, designated CeABF-1, and will provide data that will help to elucidate the molecular mechanisms that govern cell-restricted eukaryotic gene expression. This project will enhance the knowledge of target gene(s) controlled by the protein CeABF-1, and provide an understanding of the ancestral relationship between the worm CeABF-1 and human homologue, activated B-cell factor 1 (ABF-1).