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Blood, 12 February 2009, Vol. 113, No. 7, pp. 1547-1554. Prepublished online as a Blood First Edition Paper on November 13, 2008; DOI 10.1182/blood-2008-06-164954. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2008-06-164954v1 113/7/1547    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 Gallagher, P. G. Articles by Bodine, D. M. Search for Related Content PubMed PubMed Citation Articles by Gallagher, P. G. Articles by Bodine, D. M. Related Collections Red Cells, Iron, and Erythropoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS, IRON, AND ERYTHROPOIESIS An insulator with barrier-element activity promotes -spectrin gene expression in erythroid cells Patrick G. Gallagher1, Douglas G. Nilson2, Laurie A. Steiner1, Yelena D. Maksimova1, Jolinta Y. Lin2, and David M. Bodine2 1 Department of Pediatrics, Yale University School of Medicine, New Haven, CT; and 2 Hematopoiesis Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD Understanding mechanisms controlling expression of the -spectrin gene is important for understanding erythropoiesis, membrane biogenesis, and spectrin-linked hemolytic anemia. We showed previously that a minimal -spectrin promoter directed low levels of expression only in early erythroid development, indicating elements outside the promoter are required for expression in adult erythrocytes. Addition of noncoding exon 1' and intron 1' conferred a 10-fold increase in activity in reporter gene assays. In this report, we used a transgenic mouse model to show that addition of exon 1' and intron 1' to the -spectrin promoter conferred tissue-specific expression of a linked A-globin gene in erythroid cells at all developmental stages. Expression was nearly position-independent, as 21 of 23 lines expressed the transgene, and -globin protein was present in 100% of erythrocytes, indicating uniform expression. Additional in vivo studies revealed that exon 1' functions as an insulator with barrier-element activity. Chromatin immunoprecipitation assays demonstrated that this region was occupied by the upstream stimulatory factors 1/2 (USF1/USF2), similar to the well-characterized chicken HS4 insulator. These data identify the first barrier element described in an erythrocyte membrane protein gene and indicate that exon 1' and intron 1' are excellent candidate regions for mutations in patients with spectrin-linked hemolytic anemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Y. Liang, B. Moghimi, V. J. Crusselle-Davis, I-J. Lin, M. H. Rosenberg, X. Li, J. Strouboulis, S. Huang, and J. Bungert Defective Erythropoiesis in Transgenic Mice Expressing Dominant-Negative Upstream Stimulatory Factor Mol. Cell. Biol., November 1, 2009; 29(21): 5900 - 5910. [Abstract] [Full Text] [PDF] L. A. Steiner, Y. Maksimova, V. Schulz, C. Wong, D. Raha, M. C. Mahajan, S. M. Weissman, and P. G. Gallagher Chromatin Architecture and Transcription Factor Binding Regulate Expression of Erythrocyte Membrane Protein Genes Mol. Cell. Biol., October 15, 2009; 29(20): 5399 - 5412. [Abstract] [Full Text] [PDF] E. Molto, A. Fernandez, and L. Montoliu Boundaries in vertebrate genomes: different solutions to adequately insulate gene expression domains Brief Funct Genomic Proteomic, July 1, 2009; 8(4): 283 - 296. [Abstract] [Full Text] [PDF]

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