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.