Global regulation of the Hoxb complex

描述（由申请人提供）：Hox基因是一组由四个簇中的39个基因组成的基因，它们是指定片段身份的关键转录因子。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”。这可能是由于在集群中已经确定的元素，当分离出来时，已被证明概括了大部分Hox基因表达模式；然而，基因在集群中的位置似乎仍然会影响其表达特征。为了更全面地理解这些现象，我们将转座子插入覆盖大部分小鼠Hoxb簇的细菌人工染色体（BACs）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寻找调节功能的证据。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BACs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。

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.