title: The distal beta-globin CACCC box is required for maximal stimulation of the beta-globin gene by EKLF.
abstract: The transcription factor erythroid Kruppel-like factor (EKLF) specifically activates the beta-globin gene by interacting with the proximal beta-globin CACCC box, a known hot spot for thalassaemia mutations. This study investigated whether EKLF could also bind to, and activate from, the distal CACCC, which is a rare site of thalassaemia mutations. Using band shift and transient expression analysis with wild type, single and double CACCC mutants, we established that the distal CACCC box is weakly bound by EKLF, but, when mutated, significantly impairs EKLF-dependent beta-globin stimulation. Thus, EKLF requires both CACCC boxes to maximally stimulate the beta-globin gene.
authors.affiliation: Istituto di Neurogenetica e Neurofarmacologia, Universita di Cagliari, Cagliari, Italy.
authors.forename: Maria Giuseppina
authors.initials: MG
authors.lastname: Marini
authors.forename: Isadora
authors.initials: I
authors.lastname: Asunis
authors.forename: Loredana
authors.initials: L
authors.lastname: Porcu
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Salgo
authors.forename: Maria Giuseppina
authors.initials: MG
authors.lastname: Loi
authors.forename: Arianna
authors.initials: A
authors.lastname: Brucchietti
authors.forename: Antonio
authors.initials: A
authors.lastname: Cao
authors.forename: Paolo
authors.initials: P
authors.lastname: Moi
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / 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