Transcriptional regulation of GATA-3 by an intronic regulatory region and fetal liver zinc finger protein 1

J Immunol. 2002 Jul 1;169(1):248-53. doi: 10.4049/jimmunol.169.1.248.

Abstract

GATA-3 is a T cell-specific transcription factor and is essential for the development of the T cell lineage. The transcriptional regulation of GATA-3, however, remains elusive. In this study, we report the identification of a regulatory region located within the first intron of the murine GATA-3 gene. The intronic regulatory region contains both a positive and a negative cis-acting element but, as a whole, serves as a potent T cell-specific enhancer and is essential for the promoter activity in vitro. By using yeast one-hybrid screening, we discovered that fetal liver zinc finger protein 1 (Fliz1) could bind specifically to the negative cis-acting element, the sequence of which is conserved between the mouse and human GATA-3 genes. More importantly, overexpression of Fliz1 repressed the expression of GATA-3 in vivo and in vitro. Our data suggest that the expression of GATA-3 might be partly regulated by the intronic regulatory region and Fliz1 in a developmental stage-specific fashion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • COS Cells
  • Cloning, Molecular
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Epitopes, T-Lymphocyte / genetics
  • Fetus
  • GATA3 Transcription Factor
  • Humans
  • Introns / physiology*
  • Liver / embryology
  • Liver / physiology
  • Mice
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Promoter Regions, Genetic / physiology
  • Protein Binding / genetics
  • Protein Structure, Tertiary / genetics
  • RNA-Binding Proteins
  • Regulatory Sequences, Nucleic Acid / physiology*
  • Repressor Proteins / physiology
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription, Genetic / physiology*
  • Tumor Cells, Cultured
  • Zinc Fingers / genetics

Substances

  • DNA-Binding Proteins
  • Epitopes, T-Lymphocyte
  • Fliz1 protein, mouse
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Gata3 protein, mouse
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Repressor Proteins
  • Trans-Activators