MOLECULAR ANALYSIS OF A REGULATOR OF HOMEOTIC GENES

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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.