Genetic and molecular analysis of region 88E9;88F2 in Drosophila melanogaster, including the ear gene related to human factors involved in lineage-specific leukemias

Abstract

We identified and characterized the Drosophila gene ear (ENL/AF9-related), which is closely related to mammalian genes that have been implicated in the onset of acute lymphoblastic and myelogenous leukemias when their products are fused as chimeras with those of human HRX, a homolog of Drosophila trithorax. The ear gene product is present in all early embryonic cells, but becomes restricted to specific tissues in late embryogenesis. We mapped the ear gene to cytological region 88E11-13, near easter, and showed that it is deleted by Df(3R)ea5022rxl, a small, cytologically invisible deletion. Annotation of the completed Drosophila genome sequence suggests that this region might contain as many as 26 genes, most of which, including ear, are not represented by mutant alleles. We carried out a large-scale noncomplementation screen using Df(3R)ea5022rxl and chemical (EMS) mutagenesis from which we identified seven novel multi-allele recessive lethal complementation groups in this region. An overlapping deficiency, Df(3R)Po4, allowed us to map several of these groups to either the proximal or the distal regions of Df(3R)ea5022rxl. One of these complementation groups likely corresponds to the eargene as judged by map location, terminal phenotype, and reduction of EAR protein levels.