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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3412-3419. Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-05-1681. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1681v1 102/9/3412    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Katsantoni, E. Z. Articles by Strouboulis, J. Search for Related Content PubMed PubMed Citation Articles by Katsantoni, E. Z. Articles by Strouboulis, J. Related Collections Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Persistent -globin expression in adult transgenic mice is mediated by HPFH-2, HPFH-3, and HPFH-6 breakpoint sequences Eleni Z. Katsantoni, An Langeveld, Albert W. K. Wai, Dubravka Drabek, Frank Grosveld, Nicholas P. Anagnou, and John Strouboulis From the Department of Basic Sciences, University of Crete School of Medicine, Heraklion, Greece; Institute of Molecular Biology and Biotechnology, Heraklion, Greece; Department of Cell Biology and Genetics, Erasmus Medical Center, Rotterdam, The Netherlands; and the Department of Basic Sciences, University of Athens School of Medicine, Greece. Deletions at the 3' end of the human -globin locus are associated with the hereditary persistence of fetal hemoglobin (HPFH) in adults, potentially through the juxtaposition of enhancer elements in the vicinity of the fetal -globin genes. We have tested how sequences at the HPFH-2, HPFH-3, and HPFH-6 breakpoints, which act as enhancers in vitro, affect the silencing of a locus control region A (LCRA) transgene in the adult stage of mice. We found persistent A expression in the adult blood of most of the multicopy HPFH-2, HPFH-3, or HPFH-6 lines, in contrast to the control LCRA lines which were silenced. Cre-mediated generation of single copy lines showed persistent gene expression maintained in some of the HPFH-2 and HPFH-6 lines, but not in any of the HPFH-3 or LCRA lines. In the HPFH-2 and HPFH-6 lines, persistent gene expression correlated with euchromatic transgene integrations. Thus, our observations provide support for a model whereby HPFH conditions arise from the juxtaposition of enhancers as well as permissive chromatin subdomains in the vicinity of the -globin genes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Moi and M. Sadelain Towards the genetic treatment of {beta}-thalassemia: new disease models, new vectors, new cells Haematologica, March 1, 2008; 93(3): 325 - 330. [Full Text] [PDF] M. Gazouli, E. Katsantoni, T. Kosteas, and N. P. Anagnou Persistent Human {gamma}-Globin Expression in Adult Transgenic Mice Following Selective Deletion of Two Repressor Elements Located 3' to the A{gamma}-Globin Gene. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 1585 - 1585. [Abstract] [PDF] A. Bank Regulation of human fetal hemoglobin: new players, new complexities Blood, January 15, 2006; 107(2): 435 - 443. [Abstract] [Full Text] [PDF] P. Xiang, H. Han, G. Barkess, I. Olave, X. Fang, W. Yin, G. Stamatoyannopoulos, and Q. Li Juxtaposition of the HPFH2 enhancer is not sufficient to reactivate the {gamma}-globin gene in adult erythropoiesis Hum. Mol. Genet., October 15, 2005; 14(20): 3047 - 3056. [Abstract] [Full Text] [PDF] L. Chakalova, C. S. Osborne, Y.-F. Dai, B. Goyenechea, A. Metaxotou-Mavromati, A. Kattamis, C. Kattamis, and P. Fraser The Corfu {delta}{beta} thalassemia deletion disrupts {gamma}-globin gene silencing and reveals post-transcriptional regulation of HbF expression Blood, March 1, 2005; 105(5): 2154 - 2160. [Abstract] [Full Text] [PDF] P. Xiang, X. Ye, H. Han, M. Stafford, S. George, and Q. Li Juxtaposition of the HPFH2 Enhancer Is Not Sufficient To Reactivate the g-Globin Gene in Adult Erythropoiesis in bYAC Transgenic Mice. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 1215 - 1215. [Abstract]

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