Human β-globin locus control region: Analysis of the 5' DNase I hypersensitive site HS 2 in transgenic mice

Academic Article


  • The human β-globin locus control region (LCR) is essential for high-level expression of human ε-, γ-, and β-globin genes. Developmentally stable DNase I hypersensitive sites (designated HS) mark sequences within this region that are important for LCR activity. A 1.9-kilobase (kb) fragment containing the 5' HS 2 site enhances human β-globin gene expression 100-fold in transgenic mice and also confers position-independent expression. To further define important sequences within this region, deletion mutations of the 1.9-kb fragment were introduced upstream of the human β-globin gene, and the constructs were tested for activity in transgenic mice. Although enhancer activity was gradually lost with deletions of both 5' and 3' sequences, a 373-base-pair (bp) fragment retained the ability to confer relative position-independent expression. Three prominent DNase I footprints were observed in this region with extracts from the human erythroleukemia cell line K-562, one of which contained duplicated binding sites for transcription factor AP-1 (activator protein 1). When the 1.9-kb fragment containing an 18-bp deletion of the AP-1 binding sites was tested in transgenic mice, enhancer activity decreased 20-fold but position-independent expression was retained.
  • Digital Object Identifier (doi)

    Author List

  • Caterina JJ; Ryan TM; Pawlik KM; Palmiter RD; Brinster RL; Behringer RR; Townes TM
  • Start Page

  • 1626
  • End Page

  • 1630
  • Volume

  • 88
  • Issue

  • 5