HUMAN GATA-3 - A LINEAGE-RESTRICTED TRANSCRIPTION FACTOR THAT REGULATES THE EXPRESSION OF THE T-CELL RECEPTOR ALPHA-GENE

In addition to its role in the recognition of foreign antigens, the T cell receptor (TCR) alpha-gene serves as a model system for studies of developmentally-regulated, lineage-specific gene expression in T cells. TCR alpha-gene expression is restricted to cells of the TCR alpha/beta+-lineage, and is controlled by a T cell-specific transcriptional enhancer located 4.5 kb 3' to the C-alpha-gene segment. The TCR alpha-enhancer contains four nuclear protein binding sites called T-alpha-1-T-alpha-4. In this report we describe the identification and characterization of a novel human cDNA, hGATA-3 that binds to the T-alpha-3 element of the human TCR alpha-enhancer. hGATA-3 contains a zinc finger domain that is highly related to the DNA-binding domain of the erythroid-specific transcription factor, GATA-1, and binds to a region of T-alpha-3 that contains a consensus GATA binding site (AGATAG). Northern blot analyses of hematopoietic cell lines demonstrate that hGATA-3 is expressed exclusively in T cells. Overexpression of hGATA-3 in HeLa cells or human B cells specifically activated transcription from a co-transfected reporter plasmid containing two copies of the T-alpha-3 binding site located upstream of the minimal SV40 promoter. Taken together these results demonstrate that hGATA-3 is a novel lineage-specific hematopoietic transcription factor that appears to play an important role in regulating the T cell-specific expression of the TCR alpha-gene.