HASH-1 and E2-2 are expressed in human neuroblastoma cells and form a functional complex

The basic helix-loop-helix (bHLH) transcription factor mammalian achaete-sc ute homolog-1 (MASH-1 in mouse and HASH-1 in human) is essential for proper development of olfactory and most peripheral autonomic neurons, and for th e formation of distinct neuronal circuits within the central nervous system . We have previously shown that HASH-1 is expressed in neuroblastoma tumors and cell lines, and in this study we have used the yeast two-hybrid system to isolate HASH-1 interacting proteins from a human neuroblastoma cDNA lib rary. Two of the isolated clones contained cDNA from the E2-2 gene (also kn own as ITF2/ SEF2-1). We show that E2-2 interacts with HASH-1 in both yeast and mammalian cells. The HASH-1/E2-2 complex binds an E-box (CACCTG) in vi tro, and transactivates an E-box containing reporter construct in vivo. Fur thermore, E2-2 seems to be one of the major HASH-1 interacting proteins in extracts from neuroblastoma cells. In conclusion, E2-2 forms a functional c omplex with HASH-1, and might therefore be involved in the development of s pecific parts of the central and peripheral nervous systems. (C) 2000 Acade mic Press.