Title

Multiple elements in human β-globin locus control region 5′ HS 2 are involved in enhancer activity and position independent, transgene expression

Document Type

Article

Publication Date

3-25-1994

Abstract

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

First Page

1006

Last Page

1011

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