Global regulation of the Hoxb complex

Hoxb 复合体的全球调控

• 批准号: 6993267
• 负责人: MARK E PARRISH
• 金额: $ 4.4万
• 依托单位: STOWERS INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6993267
• 关键词: artificial chromosomes; developmental genetics; gene deletion mutation; gene expression; genetic enhancer element; genetic regulation; genetically modified animals; laboratory mouse; postdoctoral investigator; transcription factor; transposon /insertion element

DESCRIPTION (provided by applicant): Hox genes are a group of 39 genes in four clusters that are key transcription factors in specifying segmental identity. The expression pattern of these genes is unusual in that it correlates temporally and spatially with their position within each cluster, termed "colinearity". This could be the result of elements that have been identified within the cluster that, when isolated, have been shown to recapitulate much of Hox gene expression patterns; however, the location of a gene in the cluster still appears to influence its expression characteristics. In order to understand these phenomena more fully we have inserted transposons into bacterial artificial chromosomes (BACs) covering large portions of the murine Hoxb cluster in an effort to determine the 3' extent of elements regulating Hoxb expression. Subsequently, we are scanning these regions for evidences of regulatory function. Once identified, the in-vivo function of these elements will be interrogated by examining Hox marker gene expression from BACs in which these elements have been deleted. These experiments should provide substantial new insights into Hox gene regulation and consequently improve our understanding of segmental identity and development.

描述（由申请人提供）：Hox 基因是四个簇中的一组 39 个基因，它们是指定片段同一性的关键转录因子。这些基因的表达模式是不寻常的，因为它在时间和空间上与它们在每个簇中的位置相关，称为“共线性”。这可能是簇内已​​识别出的元素的结果，这些元素在分离时已被证明可以重现大部分 Hox 基因表达模式；然而，基因在簇中的位置似乎仍然影响其表达特征。为了更全面地理解这些现象，我们将转座子插入到覆盖小鼠 Hoxb 簇大部分的细菌人工染色体 (BAC) 中，以确定调节 Hoxb 表达的元件的 3' 范围。随后，我们正在扫描这些区域以寻找监管功能的证据。一旦确定，这些元件的体内功能将通过检查这些元件已被删除的 BAC 中的 Hox 标记基因表达来询问。这些实验应该为 Hox 基因调控提供实质性的新见解，从而提高我们对片段身份和发育的理解。