THE E2A GENE-PRODUCT CONTAINS 2 SEPARABLE AND FUNCTIONALLY DISTINCT TRANSCRIPTION ACTIVATION DOMAINS

The E2A gene encodes transcription factors of the helix-loop-helix (HL H) family which are implicated in cell-specific transcriptional contro l in several cell lineages, including pancreatic beta cells. In the pr esent work, we show by deletion mapping of both the E2A protein itself and the Gal4-E2A fusion protein that the protein contains at least tw o distinct activation domains. One domain (located between amino acids 1 and 153) functions efficiently in a variety of mammalian cell lines . The second domain (located between amino acids 369 and 485) function s preferentially in pancreatic beta cell fines. The latter domain show s a pattern of heptad repeats of leucine residues characteristic of '' leucine zipper'' transcription factors; site-directed mutagenesis of l eucines within this repeat led to substantial reductions in activity. The selective properties of this activation domain may contribute to c ell-specific transcription directed by the E2A gene.