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3 results on '"Sung-Hae Lee"'

2. Locus control region elements HS2 and HS3 in combination with chromatin boundaries confer high-level expression of a human β-globin transgene in a centromeric region

Author

Robert T. Zori, Jörg Bungert, Philip J. Laipis, Kenneth I. Berns, Sung-Hae Lee Kang, Padraic P. Levings, and Felicie F. Andersen

Subjects
Genetics, Transgene, Centromere, Mice, Transgenic, Cell Biology, Biology, Locus Control Region, Chromatin, Globins, Mice, Genetic linkage, Gene expression, Animals, Humans, Transgenes, Globin, Enhancer, Chickens, Gene, Locus control region
Abstract

Expression constructs are subject to position-effects in transgenic assays unless they harbour elements that protect them from negative or positive influences exerted by chromatin at the site of integration. Locus control regions (LCRs) and boundary elements are able to protect from position effects by preventing heterochromatization of linked genes. The LCR in the human beta-globin gene locus is located far upstream of the genes and composed of several erythroid specific DNase I hypersensitive (HS) sites. Previous studies demonstrated that the LCR HS sites act synergistically to confer position-independent and high-level globin gene expression at different integration sites in transgenic mice. Here we show that LCR HS sites 2 and 3, in combination with boundary elements derived from the chicken beta-globin gene locus, confer high-level human beta-globin gene expression in different chromosomal integration sites in transgenic mice. Moreover, we found that the construct is accessible to nucleases and highly expressed when integrated in a centromeric region. These results demonstrate that the combination of enhancer, chromatin opening and boundary activities can establish independent expression units when integrated into chromatin.

Published
2004
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3. Locus control region elements HS2 and HS3 in combination with chromatin boundaries confer high-level expression of a humanβ-globin transgene in a centromeric region.

Author

Kang, Sung-Hae Lee, Levings, Padraic P., Andersen, Felicie, Laipis, Philip J., Berns, Kenneth I., Zori, Robert T., and Bungert, Jörg

Subjects
*CHROMATIN, *GLOBIN genes, *GENE expression, *CHROMOSOMES, *TRANSGENIC mice, *NUCLEOPROTEINS
Abstract

Expression constructs are subject to position-effects in transgenic assays unless they harbour elements that protect them from negative or positive influences exerted by chromatin at the site of integration. Locus control regions (LCRs) and boundary elements are able to protect from position effects by preventing heterochromatization of linked genes. The LCR in the humanβ-globin gene locus is located far upstream of the genes and composed of several erythroid specific DNase I hypersensitive (HS) sites. Previous studies demonstrated that the LCR HS sites act synergistically to confer position-independent and high-level globin gene expression at different integration sites in transgenic mice. Here we show that LCR HS sites 2 and 3, in combination with boundary elements derived from the chickenβ-globin gene locus, confer high-level humanβ-globin gene expression in different chromosomal integration sites in transgenic mice. Moreover, we found that the construct is accessible to nucleases and highly expressed when integrated in a centromeric region. These results demonstrate that the combination of enhancer, chromatin opening and boundary activities can establish independent expression units when integrated into chromatin. [ABSTRACT FROM AUTHOR]

Published
2004
Full Text
View/download PDF

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