The human β-globin Locus Control Region (LCR) has two important activities. First, the LCR opens a 200 kb chromosomal domain containing the human ε-, γ- and β-giobin genes and, secondly, these sequences function as a powerful enhancer of ε-, γ- and β-globin gene expression. Erythrold-specific, DNase I hypersensitive sites (HS) mark sequences that are critical for LCR activity. Previous experiments demonstrated that a 1.9 kb fragment containing the 5′ HS 2 site confers position-independent expression in transgenic mice and enhances human β-giobin gene expression 100-fold. Further analysis of this region demonstrates that multiple sequences are required for maximal enhancer activity; deletion of SP1, NF-E2, GATA-1 or USF binding sites significantly decrease β-globin gene expression. In contrast, no single site is required for position- independent transgene expression; all mice with site- specific mutations in 5′ HS 2 express human β-globin mRNA regardless of the site of transgene integration. Apparently, multiple combinations of protein binding sites in 5′ HS 2 are sufficient to prevent chromosomal position effects that inhibit transgene expression. © 1994 Oxford University Press.
Publication Source (Journal or Book title)
Nucleic Acids Research
Caterina, J., Ciavatta, D., Donze, D., Behringer, R., & Townes, T. (1994). Multiple elements in human β-globin locus control region 5′ HS 2 are involved in enhancer activity and position independent, transgene expression. Nucleic Acids Research, 22 (6), 1006-1011. https://doi.org/10.1093/nar/22.6.1006