The two zinc finger-like domains of GATA-1 have different DNA binding specificities.
The GATA-1 transcription factor has been shown to be important in the regulation of globin and non-globin genes in erythroid, megakaryocytic and mast cell lineages. It is a member of a family of GATA proteins which both overlap in their expression patterns and bind the motif (A/T)GATA(A/G). The GATA family of proteins are also members of the superfamily of zinc finger-like domain proteins and have two similar domains of the type Cys-X2-Cys-X17-Cys-X2-Cys which direct the DNA binding of the protein. A random oligonucleotide selection procedure has been employed to further elucidate the mechanism of GATA-1-DNA recognition. The resulting oligonucleotides were tested for binding activity to both wild-type and mutant GATA-1 proteins. Two classes of GATA-1-DNA interaction have been defined, the first requiring only the carboxy finger of GATA-1 to bind and having the motif GAT(A/T), the second requiring both finger domains to bind and having the core motif (T/C)AAG. By using sequence comparison and depurination analysis it is concluded that the two finger-like domains of GATA-1 have different DNA binding recognition motifs. Binding of GATA-1 to GAT(A/T) motifs is associated with transcriptional activation of linked genes. The only known (T/C)AAG motif is in the distal CAAT-box promoter region of the human A gamma-globin gene where the binding of GATA-1 appears to regulate the correct developmental suppression of gamma-globin expression.
Whyatt
D J
DJ
Laboratory of Gene Structure and Expression, National Institute for Medical Research, Mill Hill, London, UK.
deBoer
E
E
Grosveld
F
F
D000818:Animals; D001483:Base Sequence; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors; D004247:DNA