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

In this report we examine the (AC)n(AT)xTy 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)xTy 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)7T5 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)7T5 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. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.