Regulation and Function of Hox gene lin-39 in C elegans

线虫Hox基因lin-39的调控与功能

• 批准号: 6578388
• 负责人: David Eisenmann
• 金额: $ 24.99万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE COUNTY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6578388
• 关键词: Caenorhabditis elegans; DNA binding protein; binding sites; biological signal transduction; gene expression; genetic regulation; genetically modified animals; homeobox genes; immunoprecipitation; microarray technology; mitogen activated protein kinase; phosphorylation; posttranslational modifications; protein structure function; regulatory gene; site directed mutagenesis

DESCRIPTION (provided by applicant): The C. elegans Hox gene lin-39 encodes a homeodomain-containing protein similar to the Drosophila Deformed and Sex Combs Reduced proteins, lin-39 is expressed in the C. elegans mid-body region, including the vulval precursor cells, and is required for the proper fate determination of these cells. In these vulval precursor cells, the tin-39 gone is coordinately regulated by both Wnt and Ras signaling pathways. We propose that the Hox gene lin-39 in C. elegans functions as a transcriptional regulator that controls the expression of a set of downstream genes in order to control the fates of the vulval precursor cells. We propose experiments to 1) determine how the Wnt and Ras pathways regulate LIN-39 protein levels, 2) identify LIN-39 binding sites in vitro and assay their relevance in vivo, 3) determine whether phosphorylation alters the functions of LIN-39 in vitro or in vivo, and 4) identify and characterize target genes regulated by L1N-39 using a microarray -based approach. Hox proteins such as LIN-39 are known to function in the patterning of cells along the anterior-posterior axis during the development of all metazoans, and defects in Hox gone expression can lead to drastic defects in development. Although Hox proteins have been characterized in many species, only a handful of target genes have been identified for these proteins. Therefore much can be learned about the function of this important class of master developmental control genes in all organisms, including humans, by the characterization of Hox protein targets in the model system C. elegans, for which full genomic sequence is available and functional genomic approaches are available.

描述（由申请人提供）：C。elegans Hox基因lin-39编码一种含有同源结构域的蛋白，类似于果蝇畸形蛋白和性梳减少蛋白。elegans中间体区域，包括外阴前体细胞，并且是这些细胞的正确命运决定所必需的。 在这些外阴前体细胞中，tin-39 gone受到Wnt和Ras信号通路的协调调节。 我们认为C.秀丽线虫作为转录调节因子发挥作用，其控制一组下游基因的表达，以控制外阴前体细胞的命运。我们提出实验来1）确定Wnt和Ras途径如何调节LIN-39蛋白水平，2）在体外鉴定LIN-39结合位点并在体内测定它们的相关性，3）确定磷酸化是否在体外或体内改变LIN-39的功能，以及4）使用基于微阵列的方法鉴定和表征由LIN-39调节的靶基因。已知Hox蛋白如LIN-39在所有后生动物发育期间沿着前后轴的细胞图案化中起作用，并且Hox gone表达的缺陷可导致发育中的严重缺陷。尽管Hox蛋白在许多物种中已被鉴定，但只有少数靶基因被鉴定为这些蛋白。因此，通过在模型系统C中表征Hox蛋白靶，可以了解这类重要的主发育控制基因在所有生物体（包括人类）中的功能。elegans，其全基因组序列是可用的，功能基因组方法是可用的。