EVIDENCE FOR A CALCIUM-REGULATED, BIDIRECTIONAL INTRONIC PROMOTER IN THE MURINE TCR V(ALPHA)1 GENE

Previous studies of the TCR alpha chain gene have located promoter ele ments 5' to the start of the various V-alpha genes. The only fully cha racterized enhancer for the entire alpha chain gene (V, J and C genes) has been located similar to 3 kb from the 3' end of C-alpha. We now r eport the existence of additional regulatory elements located in the i ntrons of several murine V-alpha genes (V(alpha)1, V(alpha)3 and V(alp ha)86,2,16). In the case of V(alpha)1, this element appears to be a pr omoter with bidirectional activity that is not T cell specific. Intere stingly, upstream of the promoter in the antisense strand, an open rea ding frame has been found that codes for a small molecular weight prot ein (similar to 60 amino acids) that contains a proline-rich region an d a tyrosine-isoleucine motif that has homology to Ig beta (the B29 ge ne product). A rabbit antiserum made against this sequence has confirm ed its existence by Western blot and immunoprecipitation. Thus this V( alpha)1 intronic promoter has the potential not only to induce the for mation of a truncated V(alpha)1 gene product, but also regulates the e xpression of a small molecular weight protein that may be involved in lymphocyte antigen receptor signaling. The activity of this promoter i s regulated by changes in intracellular calcium. In the presence of io nomycin the promoter is down-regulated in the sense direction and its activity is enhanced in the antisense direction. This result suggests that this promoter can act differentially to produce two very differen t gene products. The bidirectional V(alpha)1 promoter appears to be th e first in the Ig superfamily to induce potentially functional protein s in both directions.