HMG-I binds to GATA motifs: implications for an HPFH syndrome.
We have examined binding of the nuclear protein HMG-I to the human gamma-globin promoter. We find that HMG-I binds preferentially to the more 3' of a pair of GATA motifs in the gamma-globin promoter; this paired motif is bound by the erythroid factor GATA-1. A naturally occurring mutation (-175 T-C) in the area bound by HMG-I results in overexpression of gamma-globin in adult red blood cells (HPFH) and up-regulation of the gamma-globin promoter in in vitro expression assays; HMG-I does not bind to this mutant sequence. A survey of GATA motifs from other globin cis-elements demonstrates HMG-I binding to most of them. These findings implicate HMG-I in the HPFH phenotype; we speculate that it may participate in the formation of multiprotein complexes that regulate globin gene expression.
Magis
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University of Washington School of Medicine, Seattle, USA.
Martin
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D000328:Adult; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D005319:Fetal Hemoglobin / Q000235:genetics / Q000378:metabolism; D050982:GATA1 Transcription Factor; D005786:Gene Expression Regulation; D005914:Globins / Q000096:biosynthesis* / Q000235:genetics*; D006453:Hemoglobinopathies / Q000235:genetics*; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D006609:High Mobility Group Proteins; D015345:Oligonucleotide Probes; D014157:Transcription Factors; D005914:Globins; D005319:Fetal Hemoglobin