Transcriptional regulation of GATA-3 by an intronic regulatory region and fetal liver zinc finger protein 1.
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.
Hwang
Eun Sook
ES
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Choi
Andrew
A
Ho
I-Cheng
IC
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005333:Fetus; D050990:GATA3 Transcription Factor; D006801:Humans; D007438:Introns / Q000502:physiology*; D008099:Liver / Q000196:embryology / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D016601:RNA-Binding Proteins; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; C432964:Fliz1 protein, mouse; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494748:Gata3 protein, mouse; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D015534:Trans-Activators