A T-cell specific TCR delta DNA binding protein is a member of the human GATA family

Abstract

The human GATA1, hGATA1 (previously called NF-E1, GF-1 or Eryf-1), a major sequence-specific DNA-binding protein of the erythrocytic lineage, is a member of a zinc-finger family of DNA-binding proteins. We report here the cloning of a human cDNA for a new member of this family. This member, called hGATA3, has 85% amino acid homology with hGATA1 in the DNA-binding domain and no homology elsewhere in the protein. Unlike hGATA1, hGATA3 is not localized on the X chromosome and we map it to the 10p15 band of the human genome. Northern blot analysis indicates that this factor is a T-cell specific transcription factor, present before activation and up-regulated during T-cell activation. The encoded hGATA3 protein, made in an in vitro transcription-translation assay, binds the WGATAR motif present in the human T-cell receptor (TCR) delta gene enhancer and, by transfection in HeLa cells, we show that hGATA3 can transactivate this TCR delta gene enhancer. Interestingly this enhancer binds and is also transactivated by hGATA1. Conversely, the promoter of the human glycophorin B (GPB), which is erythroid-specific and contains two WGATAR motifs, binds and is transactivated by hGATA1 and, to a lesser extent, by hGATA3. These results indicate that the activation of specific genes by hGATA1 or hGATA3 is partly governed by the lineage expression of these two factors during haematopoiesis and that, in the T-cell lineage, hGATA3 binds the human TCR delta gene enhancer and is involved in its expression.