The distal beta-globin CACCC box is required for maximal stimulation of the beta-globin gene by EKLF.
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.
Marini
Maria Giuseppina
MG
Istituto di Neurogenetica e Neurofarmacologia, Universita di Cagliari, Cagliari, Italy.
Asunis
Isadora
I
Porcu
Loredana
L
Salgo
Maria Giulia
MG
Loi
Maria Giuseppina
MG
Brucchietti
Arianna
A
Cao
Antonio
A
Moi
Paolo
P
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
D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor; D005914:Globins