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
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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COS Cells
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Cloning, Molecular
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Epitopes, T-Lymphocyte / genetics
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Fetus
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GATA3 Transcription Factor
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Humans
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Introns / physiology*
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Liver / embryology
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Liver / physiology
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Mice
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Mice, Inbred ICR
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Mice, Transgenic
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Nuclear Proteins / physiology*
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Promoter Regions, Genetic / physiology
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Protein Binding / genetics
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Protein Structure, Tertiary / genetics
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RNA-Binding Proteins
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Regulatory Sequences, Nucleic Acid / physiology*
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Repressor Proteins / physiology
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / genetics*
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Trans-Activators / metabolism
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Transcription, Genetic / physiology*
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Tumor Cells, Cultured
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Zinc Fingers / genetics
Substances
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DNA-Binding Proteins
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Epitopes, T-Lymphocyte
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Fliz1 protein, mouse
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GATA3 Transcription Factor
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GATA3 protein, human
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Gata3 protein, mouse
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Nuclear Proteins
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RNA-Binding Proteins
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Repressor Proteins
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Trans-Activators