STRUCTURE AND EXPRESSION PATTERN OF HUMAN ALR, A NOVEL GENE WITH STRONG HOMOLOGY TO ALL-1 INVOLVED IN ACUTE-LEUKEMIA AND TO DROSOPHILA-TRITHORAX

The ALL-1 gene is involved in human acute leukemia through chromosome translocations or internal rearrangements. ALL-1 is the human homologu e of Drosophila trithorax. The latter is a member of the trithorax gro up (trx-G) genes which together with the Polycomb group (Pc-G) genes a ct as positive and negative regulators, respectively, to determine the body structure of Drosophila. We have cloned a novel human gene, ALR, which encodes a gigantic 5262 amino acid long protein containing a SE T domain, five PHD fingers, potential zinc fingers, and a very long ru n of glutamines interrupted by hydrophobic residues, mostly leucine. T he SET motif, PDH fingers, zinc fingers and two other regions are most similar to domains of ALL-1 and TRX. The first two motifs are also fo und in other trx-G and Pc-G proteins. The ALR gene was mapped to chrom osome band 12q12-13, adjacent to the VDR gene. This region is involved in duplications and translocations associated with cancer. The analys is of ALR expression showed that its similar to 18 kb long mRNA is exp ressed, like ALL-1, in most adult tissues, including a variety of hema topoietic cells, with the exception of the liver. Whole mount in situ hybridization to early mouse embryos indicates expression in multiple tissues. Based on similarities in structure and expression pattern, AL R is likely to play a similar role to ALL-1 and trx, although its targ et genes have yet to be identified.