MULTIPLE ISOFORMS OF GAGA FACTOR, A CRITICAL COMPONENT OF CHROMATIN STRUCTURE

The GAGA transcription factor of Drosophila melanogaster is ubiquitous and plays multiple Poles. Characterization of cDNA clones and detecti on by domain-specific antibodies has revealed that the 70-90 kDa major GAGA species are encoded by two open reading frames producing GAGA fa ctor proteins of 519 amino acids (GAGA-519) and 581 amino acids (GAGA- 581), which share a common N-terminal region that is linked to two dif ferent glutamine-rich C-termini, Purified recombinant GAGA-519 and GAG A-581 proteins can form homomeric complexes that bind specifically to a single GAGA sequence in vitro, The two GAGA isoforms also function s imilarly in transient transactivation assays in tissue culture cells a nd in chromatin remodeling experiments in vitro, Only GAGA-519 protein accumulates during the first 6 h of embryogenesis. Thereafter, both G AGA proteins are present in nearly equal amounts throughout developmen t; in larval salivary gland nuclei they colocalize completely to speci fic regions along the euchromatic arms of the polytene chromosomes, Co immunoprecipitation of GAGA-519 and GAGA-581 from crude nuclear extrac ts and from mixtures of purified recombinant proteins, indicates direc t interactions, We suggest that homomeric complexes of GAGA-519 may fu nction during early embryogenesis; both homomeric and heteromeric comp lexes of GAGA-519 and GAGA-581 may function later.