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Publication : Analysis of mice containing a targeted deletion of beta-globin locus control region 5' hypersensitive site 3.

First Author  Hug BA Year  1996
Journal  Mol Cell Biol Volume  16
Issue  6 Pages  2906-12
PubMed ID  8649401 Mgi Jnum  J:33053
Mgi Id  MGI:80540 Doi  10.1128/mcb.16.6.2906
Citation  Hug BA, et al. (1996) Analysis of mice containing a targeted deletion of beta-globin locus control region 5' hypersensitive site 3. Mol Cell Biol 16(6):2906-12
abstractText  To examine the function of murine beta-globin locus control region (LCR) 5' hypersensitive site 3 (HS3) in its native chromosomal context, we deleted this site from the mouse germ line by using homologous recombination techniques. Previous experiments with human 5' HS3 in transgenic models suggested that this site independently contains at least 50% of total LCR activity and that it interacts preferentially with the human gamma-globin genes in embryonic erythroid cells, However, in this study, we demonstrate that deletion of murine 5' HS3 reduces expression of the linked embryonic epsilon gamma- and PH 1- globin genes only minimally in yolk sac-derived erythroid cells and reduces output of the linked adult beta (beta major plus beta minor) globin genes by approximately 30% in adult erythrocytes. When the selectable marker PGK-neo cassette was left within the HS3 region of the LCR, a much more severe phenotype was observed at all developmental stages, suggesting that PGk=neo interferes with LCR activity when it is retained within the LCR. Collectively, these results suggest that murine 5' HS3 is not required for globin gene switching; importantly, however, it is required for approximately 30% of the total LCR activity associated with adult beta-globin gene expression in adult erythrocytes.
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