The erythroid-specific protein cGATA-1 mediates distal enhancer activity through a specialized beta-globin TATA box.
The erythroid-specific protein cGATA-1 regulates the chick beta-globin gene through GATA sequences present at the canonical TATA location in the promoter as well as the distal 3' enhancer. We have analyzed beta-globin transcription in transfected erythroid cells and in erythroid extracts to determine whether cGATA-1 binding at -30 regulates promoter or enhancer activity. The interaction of both cGATA-1 and TFIID at different times with the -30 GATA site is required for efficient beta-globin expression in vivo, and the GATA enhancer site can functionally replace the TATA element in the beta-globin promoter. TFIID initiates transcription in vitro by complexing with adaptor proteins and displacing cGATA-1 from the -30 GATA site. Mutations that abolish TFIID binding to the -30 GATA box inactivate the promoter, whereas elimination of cGATA-1 binding to this site selectively diminishes enhancer-dependent transcription. We propose that interaction of cGATA-1 with the distal 3' enhancer and the specialized TATA box confers erythroid specificity to the initiation complex by mediating promoter-enhancer communication. Thus, one mechanism of action for tissue-specific proteins that recognizes noncanonical TATA motifs is to enable TFIID to be regulated by distal control elements. In this way, the initiation complex can be responsive to specific regulators that may not recognize a canonical TFIID-TATA structure.
Fong
T C
TC
Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037.
Emerson
B M
BM
D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D050981:Erythroid-Specific DNA-Binding Factors; D005914:Globins / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016385:TATA Box; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D014157:Transcription Factors; D005914:Globins