The study of sequence configuration and functional impact of the (AC) n(AT) xT y motif in human β-globin gene promoter

Abstract

In this report we examine the (AC) n(AT) xT y motif residing -530 bp 5′ upstream of the β-globin gene in Chinese thalassaemic patients. This motif is a putative binding site for a repressor protein, termed beta protein 1 (BP1) (Berg et al., Nucleic Acids Res 1989;17:8833-8852). Variations in the (AC) n(AT) xT y repeats affect the binding affinity of BP1, thereby altering the expression of the β-globin gene. Eight different configurations of this repeat motif are identified in our population of Chinese β-thalassaemia patients. A (AC) 3(AT) 7T 5 motif was identified among these thalassaemia patients and its influence in β-globin gene expression was studied using stable transfection assay in murine erythroleukemia (MEL) cells. Our data demonstrated that the (AC) 3(AT) 7T 5 motif has a moderately strong repressor effect on the expression of the cis-linked β-globin gene. The high affinity of BP1 for this motif may result in the suppression of the transcription of the β-globin gene (Berg et al., Am J Hematol 1991;36:42-47). We postulate that silencer elements in the β-globin promoter play an important role in modifying the clinical presentation of the disease. © 2006 Wiley-Liss, Inc.