title: The study of sequence configuration and functional impact of the (AC)n(AT)xTy motif in human beta-globin gene promoter.
abstract: In this report we examine the (AC)n(AT)xTy motif residing -530 bp 5' upstream of the beta-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 beta-globin gene. Eight different configurations of this repeat motif are identified in our population of Chinese beta-thalassaemia patients. A (AC)3(AT)7T5 motif was identified among these thalassaemia patients and its influence in beta-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 beta-globin gene. The high affinity of BP1 for this motif may result in the suppression of the transcription of the beta-globin gene (Berg et al., Am J Hematol 1991;36:42-47). We postulate that silencer elements in the beta-globin promoter play an important role in modifying the clinical presentation of the disease.
authors.affiliation: Department of Zoology, Kadoorie Biological Science Building, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
authors.forename: P K
authors.initials: PK
authors.lastname: Chan
authors.forename: E S K
authors.initials: ES
authors.lastname: Ma
authors.forename: S
authors.initials: S
authors.lastname: Philipsen
authors.forename: K C
authors.initials: KC
authors.lastname: Tan-Un
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005319:Fetal Hemoglobin / Q000032:analysis; D005786:Gene Expression Regulation; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D018398:Homeodomain Proteins / Q000378:metabolism; D006723:Hong Kong; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism; D037941:Silencer Elements, Transcriptional / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D017086:beta-Thalassemia / Q000208:ethnology / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; C105304:DLX4 protein, human; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D005914:Globins; D005319:Fetal Hemoglobin