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The study of sequence configuration and functional impact of the (AC) n (AT) x T y motif in human β‐globin gene promoter
Author(s) -
Chan P.K.,
Ma E.S.K.,
Philipsen S.,
TanUn K.C.
Publication year - 2007
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.20836
Subject(s) - globin , gene , microbiology and biotechnology , repressor , biology , transcription (linguistics) , transfection , sequence motif , genetics , gene expression , linguistics , philosophy
In this report we examine the (AC) n (AT) x T 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) x T 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) 7 T 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) 7 T 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. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.