Regulation of the stem cell leukemia (SCL) gene: A tale of two fishes

The stem cell leukemia (SQ) gene encodes a tissue-specific basic helix-loop -helix (bHLH) protein with a pivotal role in hemopoiesis and vasculogenesis . Several enhancers have been identified within the murine SCL locus that d irect reporter gene expression to subdomains of the normal SCL expression p attern, and long-range sequence comparisons of the human and murine SCL loc i have identified additional candidate enhancers. To facilitate the charact erization of regulatory elements, we have sequenced and analyzed 33 kb of t he SCL genomic locus from the pufferfish Fugu rubripes, a species with a hi ghly compact genome. Although the pattern of SCL expression is highly conse rved from mammals to teleost fish, the genes flanking pufferfish SCL were u nrelated to those known to flank both avian and mammalian SCL genes. These data suggest that SCL regulatory elements are confined to the region betwee n the upstream and downstream flanking genes, a region of 65 kb in human an d 8.5 kb in pufferfish, Consistent with this hypothesis, the entire 33-kb p ufferfish Sa locus directed appropriate expression to hemopoietic and neura l tissue in transgenic zebrafish embryos, as did a 10.4-kb fragment contain ing the SQ gene and extending to the 5' and 3' flanking genes. These result s demonstrate the power of combining the compact genome of the pufferfish w ith the advantages that zebrafish provide for studies of gene regulation du ring development. Furthermore, the pufferfish SCL locus provides a powerful tool for the manipulation of hemopoiesis and vasculogenesis in vivo.