MOLECULAR ANALYSIS OF A REGULATOR OF HOMEOTIC GENES

许多动物胚胎的身体平面图有两个共同的要素： 基本的分段结构，并叠加在它上面， 选择基因或同源异型基因家族。 这些基因编码同源结构域- 一类赋予独特形态特征的转录因子 通过调节转录， 下游的靶基因。 反过来，同源异型基因必须 在时间和空间上都得到精确的调节， 有机体的发展。 在果蝇中，同源基因 被限制在两个复合体中，即双足（ANT-C）和双胸（BX-C）， 已经报道了同源异型基因的三个水平的控制。 这些是 分段基因的调控， ANT-C和BX-C内的基因，以及Polycomb 群和三胸群基因。 监管系统控制着 同源异型基因的表达在动物中似乎是高度保守的 因此，已经发现了Polycomb基因的小鼠同源物 最近的研究表明，人类同源基因的畸变 是儿童白血病的最常见原因。 该项目的长期目标是了解 维持同源异型基因和其他发育基因的表达 在果蝇的发育过程中。 特别是，这项研究 将集中在三胸（trx）的分子组织和功能， 一种参与同源异型和其它基因的反式调节的基因。 空间 和时间分布的trx蛋白产物从早期的 胚胎到后期劳拉将被确定。 功能意义 Trx蛋白结构域及其与 将分析哺乳动物ALL-1。 我们将识别trx响应 同源异型基因forkhead和 我们将继续寻找未知的trx靶点， vivo. 其他trx-组和基因所需的相互作用， 将鉴定靶基因。

The body plans of many animal embryos have two elements in common: a basic segmented structure and, superimposed on it, the expression of a family of selector, or homeotic, genes. These genes encode homeodomain- class transcription factors that assign unique identities morphological characteristics to individual segments by regulating the transcription of downstream target genes. In turn, the homeotic genes must be precisely regulated, both temporally and spatially, the ensure normal development of the organism. In Drosophila, where homeogenes are confined within two complexes, Antennapedia (ANT-C) and Bithorax )BX-C), three levels of control of homeotic genes have been reported. These are regulation by segmentation genes, cross-regulatory interactions among genes within the ANT-C and BX-C, and transregulation by the Polycomb group and trithorax group genes. The regulatory systems that control homeotic gene expression appear to be highly conserved in the animal kingdom, thus, the mouse homologue of the Polycomb gene has been found and, more recently, it has been shown that aberrations in human homologue of trx is the most common cause of leukemias in children. The long term goal of this project is to understand molecular basis of maintenance of the expression of homeotic and other developmental genes throughout Drosophila development. In particular, this proposed research will focus on molecular organization and functions of trithorax (trx), a gene involved in transregulation of homeotic and other genes. Spatial and temporal distribution of the trx protein products from the early embryo to the late lara will be determined. Functional significance of the trx protein domains and their relevance to the structure of the mammalian ALL-1 will be analysed. We will identify trx responsive elements in the regulatory regions of the homeotic genes forkhead and Ultrabithorax and continue our search for yet unknown targets of trx in vivo. Other trx-group and genes required for its interactions with target genes will be identified.