REGULATION OF GENES CONTROLLING ABDOMINAL DEVELOPMENT

控制腹部发育的基因调控

• 批准号: 2203067
• 负责人: EDWARD B LEWIS
• 金额: $ 13.93万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2203067
• 关键词: DNA; Drosophilidae; abdomen; cell differentiation; developmental genetics; gene deletion mutation; gene expression; genetic disorder; genetic library; genetic mapping; genetic promoter element; genetic regulatory element; histochemistry /cytochemistry; homeobox genes; in situ hybridization; molecular cloning; nucleic acid probes; nucleic acid sequence; polymerase chain reaction; southern blotting

The broad long-term objective is to understand at the molecular level how a gene cluster of the bithorax type is able to program the development of the body segments of higher organisms. This proposal focuses on the Abdominal-B (Abd-B) domain of the bithorax complex (BX-C) and more specifically on how it is regulated in cis. Several features of the organization of the cis-regulatory regions of this domain are highly unusual: a) over 95% of the DNA of the Abd-B domain exists in such regions; b) over 50% of these regions are located 3' rather than 5' to the coding region; and c) the regions are colinear in their chromosome order with their order of controlling Abd-B protein expression along the body axis. Our specific aims are l) to develop new tools for dissecting various classes of elements within each cis-regulatory region; 2) to correlate the morphological effects of varying length deletions of these regions with the effects of such deletions upon the pattern of Abd-B expression; 3) to use transformation assays based on P-element constructs to discover classes of elements that are responsible for the wild-type pattern of Abd- B expression and; 4) to undertake a computational analysis of DNA sequence in the cis-regulatory regions to search for redundancy of specific motifs. These aims will enable us to test the hypothesis that there are elements within each 3'cis-regulatory region that cause one of the ABD-B proteins (ABD-BI) to be expressed in a graded fashion that increases along the anterior/posterior body axis. A more global hypothesis that we plan to test with our studies is that the cis-regulatory regions have evolved from an ancestral region by tandem duplication and subsequent diversification by mutation. Our proposed studies are expected to have application to the molecular characterization of a variety of human genetic defects that involve faulty regulation of homeobox genes. In addition, there are expected to be applications to characterizing underlying defects that are responsible for tumorigenesis.

广泛的长期目标是在分子水平上了解如何 双胸型的基因簇能够编程 高等生物的身体部分。该提案的重点是 双胸复合体 (BX-C) 的腹部 B (Abd-B) 结构域等 特别是关于独联体国家如何对其进行监管。的几个特点 该域的顺式监管区域的组织高度 不寻常：a) 超过 95% 的 Abd-B 结构域 DNA 存在于这样的结构中 地区； b) 超过 50% 的这些区域位于 3' 而不是 5' 处 编码区； c) 这些区域在染色体顺序上是共线的 以及它们控制 Abd-B 蛋白在体内表达的顺序 轴。我们的具体目标是 l) 开发新工具来剖析各种 每个顺式监管区域内的元素类别； 2）关联 这些区域的不同长度缺失的形态学影响 此类缺失对 Abd-B 表达模式的影响； 3）到 使用基于 P 元素构建体的转化分析来发现 负责 Abd- 野生型模式的元素类别 B 表达式和； 4) 对DNA序列进行计算分析 在顺式调控区域中寻找特定基序的冗余。 这些目标将使我们能够检验存在元素的假设 在导致 ABD-B 蛋白之一的每个 3' 顺式调控区域内 （ABD-BI）以分级方式表示，随着 前/后身体轴。我们计划提出一个更加全球性的假设 我们的研究测试表明，顺式调控区域是从 通过串联复制和随后的多样化形成的祖先区域 通过突变。 我们提出的研究预计将应用于 多种人类遗传缺陷的分子特征 涉及同源盒基因的错误调节。此外，还有 预计将成为表征潜在缺陷的应用程序 负责肿瘤发生。