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

Am J Hematol. 2007 May;82(5):342-8. doi: 10.1002/ajh.20836.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics*
  • Animals
  • Binding Sites
  • Cell Differentiation
  • Cell Line, Tumor
  • Fetal Hemoglobin / analysis
  • Gene Expression Regulation
  • Globins / biosynthesis
  • Globins / genetics*
  • Homeodomain Proteins / metabolism
  • Hong Kong
  • Humans
  • Leukemia, Erythroblastic, Acute / pathology
  • Mice
  • Promoter Regions, Genetic / genetics*
  • Repressor Proteins / metabolism
  • Silencer Elements, Transcriptional / genetics*
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transfection
  • beta-Thalassemia / ethnology
  • beta-Thalassemia / genetics*


  • 5' Untranslated Regions
  • DLX4 protein, human
  • Homeodomain Proteins
  • Repressor Proteins
  • Transcription Factors
  • Globins
  • Fetal Hemoglobin