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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3346-3352. Prepublished online as a Blood First Edition Paper on December 30, 2004; DOI 10.1182/blood-2004-03-0987. This Article Full Text (PDF) All Versions of this Article: 2004-03-0987v1 105/8/3346    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Li, Q. Articles by Stamatoyannopoulos, G. Search for Related Content PubMed PubMed Citation Articles by Li, Q. Articles by Stamatoyannopoulos, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 18, 2004 Accepted December 20, 2004 Differences of globin transgene expression in stably transfected cell lines and transgenic mice Qiliang Li*, David W Emery, Hemei Han, Jin Sun, Man Yu, and George Stamatoyannopoulos Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA, USA * Corresponding author; email: li111640{at}u.washington.edu. Previous studies demonstrated that DNase I hypersensitive site -40 (HS-40) of the alpha-globin locus is capable of greatly enhancing expression of a hybrid /-globin transcriptional unit in plasmid transfected MEL cells. However, as reported here, this same -globin gene expression cassette was only transcribed at trace amounts in erythroid cells of transgenic mice. This lack of expression was not directly attributable to the /-globin transcriptional unit, since this same unit linked to a composite -globin locus control region was expressed at high levels in transgenic mice. This lack of expression was also not directly attributable to chromosomal position effects, since addition of chromatin insulators failed to increase the frequency of expression. DNase I hypersensitivity and chromatin immunoprecipitation assays demonstrated that the lack of expression was correlated with a closed chromatin structure. We hypothesize that transgenes undergo dynamic changes in chromatin conformation following chromosomal integration, and that the discrepant results reported here can be attributed to the relatively high level of chromatin remodeling which occurs in the transgenic mouse model, coupled with the relative inability of the HS-40 element to maintain an open chromatin state under such conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Lisowski and M. Sadelain Locus control region elements HS1 and HS4 enhance the therapeutic efficacy of globin gene transfer in -thalassemic mice Blood, December 15, 2007; 110(13): 4175 - 4178. [Abstract] [Full Text] [PDF]

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