SEQUENCE-SPECIFIC PROTEIN-INTERACTION WITH A TRANSCRIPTIONAL ENHANCERINVOLVED IN THE AUTOREGULATED EXPRESSION OF CAMP RECEPTOR-1 IN DICTYOSTELIUM

Major stages of Dictyostelium development are regulated by secreted, e xtracellular cAMP through activation of a serpentine receptor family. During early development, oscillations of extracellular cAMP mobilize cells for aggregation; later, continuous exposure to higher extracellu lar cAMP concentrations downregulates early gene expression and promot es cytodifferentiation and cell-specific gene expression. The cAMP rec eptor 1 gene CAR1 has two promoters that are differentially responsive to these extracellular cAMP stimuli. The early CAR1 promoter is induc ed by nM pulses of cAMP, which in turn are generated by CAR1-dependent activation of adenylyl cyclase (AC). Higher, non-fluctuating concentr ations of cAMP will adapt this AC stimulus-response, repress the activ ated early promoter and induce the dormant late promoter, We now ident ify a critical element of the pulse-induced CAR1 promoter and a nuclea r factor with sequence-specific interaction. Mutation of four nucleoti des within the element prevents both in vitro protein binding and in v ivo expression of an otherwise fully active early CAR1 promoter and mu ltimerization of the wild-type, but not mutant, sequence will confer c AMP regulation to a quiescent heterologous promoter. These cis and tra ns elements, thus, constitute a part of the molecular response to the cAMP transmembrane signal cascade that regulates early development of Dictyostelium.