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

Journal Article · Fri Mar 01 00:00:00 EST 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.5.1626· OSTI ID:6396675

Caterina, J J; Ryan, T M; Pawlik, K M; Townes, T M ^[1]; Brinster, R L ^[2]; Behringer, R R ^[3]; Palmiter, R D ^[4]

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1. Univ. of Alabama, Birmingham (United States)
2. Univ. of Pennsylvania, Philadelphia (United States)
3. Univ. of Pennsylvania, Philadelphia (United States) Univ. of Texas, Houston (United States)
4. Univ. of Washington, Seattle (United States)

The human {beta}-globin locus control region (LCR) is essential for high-level expression of human {var epsilon}-, {gamma}-, and {beta}-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{prime} HS 2 site enhances human {beta}-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 {beta}-globin gene, and the constructs were tested for activity in transgenic mice. Although enhancer activity was gradually lost with deletion of both 5{prime} and 3{prime} 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 19-bp deletion of the AP-1 binding sites was tested in transgenic mice, enhancer activity decreased 20-fold but position-independent expression was retained.

• OSTI ID: 6396675
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:5; ISSN 0027-8424
• Country of Publication: United States
• Language: English

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