title: A novel silent beta-thalassemia mutation in the distal CACCC box affects the binding and responsiveness to EKLF.
abstract: The silent beta-thalassemia mutation, beta(+)-101C-->T, is the only mutation currently described in the distal beta-globin CACCC box. We present a novel mutation, a C-->G transversion, in the same position. Expression analysis in heterozygous subjects demonstrated that the mutation determines a 20% reduction in the output of the beta-globin gene. DNA-protein interaction and transactivation analysis correlated the decrease in the beta-globin synthesis with the reduced binding and transactivation of EKLF to the mutant promoter. These data predict that the beta-101C-->G mutation will display a silent thalassemia phenotype similar to that of the beta-101C-->T mutation.
authors.affiliation: Dipartimento di Scienze Biomediche e Biotecnologie, Universita' di Cagliari.
authors.forename: Paolo
authors.initials: P
authors.lastname: Moi
authors.forename: Valeria
authors.initials: V
authors.lastname: Faà
authors.forename: Maria Giuseppina
authors.initials: MG
authors.lastname: Marini
authors.forename: Isadora
authors.initials: I
authors.lastname: Asunis
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ibba
authors.forename: Antonio
authors.initials: A
authors.lastname: Cao
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Rosatelli
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D017086:beta-Thalassemia / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor; D005914:Globins