GATA-binding transcription factors in mast cells regulate the promoter of the mast cell carboxypeptidase A gene.
The transcription factors GATA-1, GATA-2, and GATA-3 were found to be expressed in several mouse and rat mast cell lines that contain mast cell carboxypeptidase A (MC-CPA) and other proteases in their cytoplasmic granules. GATA-1 mRNA was not detected in P815 cells, an immature mouse mastocytoma-derived cell line that lacks electron-dense granules and has low levels of secretory granule proteases. Because the 5'-flanking regions of the mouse and human MC-CPA genes contained a conserved GATA-binding motif 51 base pairs upstream of their translation initiation sites, the ability of GATA-binding proteins to regulate the promoter activity of the MC-CPA gene was examined in rat basophilic leukemia cells, mouse P815 cells, and transfected mouse P815 cells that expressed GATA-1. In all three mast cell lines, the promoter activity of the MC-CPA gene depended on the GATA binding site. GATA-1, GATA-2, and GATA-3 are thus the first DNA-binding proteins identified in mast cells which regulate the promoter activity of a gene that encodes a secretory granule protease.
Zon
L I
LI
Department of Pediatrics, Harvard Medical School, Children's Hospital, Boston, Massachusetts 02115.
Gurish
M F
MF
Stevens
R L
RL
Mather
C
C
Reynolds
D S
DS
Austen
K F
KF
Orkin
S H
SH
D000818:Animals; D001483:Base Sequence; D002268:Carboxypeptidases / Q000235:genetics* / Q000378:metabolism; D043422:Carboxypeptidases A; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D015971:Gene Expression Regulation, Enzymologic; D008407:Mast Cells / Q000201:enzymology*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D051381:Rats; D015534:Trans-Activators / Q000096:biosynthesis / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; C494689:Gata1 protein, mouse; C494690:Gata1 protein, rat; C494712:Gata2 protein, mouse; C494713:Gata2 protein, rat; C494748:Gata3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D002268:Carboxypeptidases; D043422:Carboxypeptidases A