Transcriptional up-regulation of the mouse cytosolic glutathione peroxidase gene in erythroid cells is due to a tissue-specific 3' enhancer containing functionally important CACC/GT motifs and binding sites for GATA and Ets transcription factors.
Nuclear run-on experiments have shown that the high level of expression of the mouse cytosolic glutathione peroxidase mRNA in erythroid cells is due to up-regulation of the gene at the transcriptional level. Studies of the chromatin structure around the cytosolic glutathione peroxidase gene have revealed a series of DNase I hypersensitive sites (DHSS) in the 3' flanking region of the gene in erythroid and other high-expression tissues that are lacking in low-expression cells, in addition to a DHSS over the promoter region in both high- and low-expression tissues. Functional transfection experiments have demonstrated that one of the 3' DHSS regions functions as an enhancer in erythroid cells but not in a low-expression epithelial cell line; and site-directed mutagenesis and footprinting experiments reveal that the activity of the erythroid cell-specific enhancer requires a cluster of binding sites for the CACC/GT box factors and the GATA and Ets families of transcription factors.
O'Prey
J
J
Beatson Institute for Cancer Research, Cancer Research Campaign Beatson Laboratories, Bearsden, Glasgow, Scotland.
Ramsay
S
S
Chambers
I
I
Harrison
P R
PR
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003600:Cytosol / Q000201:enzymology; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism; D003850:Deoxyribonuclease I; D004742:Enhancer Elements, Genetic; D004912:Erythrocytes / Q000166:cytology / Q000201:enzymology*; D050981:Erythroid-Specific DNA-Binding Factors; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009928:Organ Specificity / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D015183:Restriction Mapping; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D004247:DNA; D005979:Glutathione Peroxidase; D003850:Deoxyribonuclease I