GATA ELEMENTS ARE NECESSARY FOR THE ACTIVITY AND TISSUE-SPECIFICITY OF THE T-CELL RECEPTOR BETA-CHAIN TRANSCRIPTIONAL ENHANCER

Three high-affinity binding sites for the GATA family of transcription al regulators have been identified within the T-cell receptor beta-cha in (TCR beta) transcriptional enhancer, and their functional significa nce has been determined in an effort to understand the T-cell specific ity of the enhancer more fully. One site, TE4, is important for activi ty of the enhancer in T cells. Neither site TE1 nor site TE2 can funct ionally replace a mutated TE4 site in T cells; however, the same prote in, probably GATA-3, binds all three sites, as judged by electrophoret ic mobility shift, oligonucleotide competition, and proteolytic clippi ng assays. These data suggest that additional proteins are critical fo r the ability of GATA-3 to activate the TCR beta enhancer. In fibrobla sts, the GATA sequence at site TE1 appears to bind a negative regulato r. Since this is not true in B cells, B cells and fibroblasts appear t o have different mechanisms for negative regulation of the TCR beta en hancer.