Human GATA-3: a lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene

EMBO J. 1991 May;10(5):1187-92. doi: 10.1002/j.1460-2075.1991.tb08059.x.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • DNA / chemistry
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • Enhancer Elements, Genetic
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • HeLa Cells / metabolism
  • Humans
  • Molecular Sequence Data
  • Multigene Family
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Tumor Cells, Cultured
  • Zinc Fingers / genetics*

Substances

  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Transcription Factors
  • DNA

Associated data

  • GENBANK/X55037