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Blood, 15 January 2006, Vol. 107, No. 2, pp. 821-826. Prepublished online as a Blood First Edition Paper on September 27, 2005; DOI 10.1182/blood-2005-06-2308. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-06-2308v1 107/2/821    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 Hu, X. Articles by Fiering, S. Search for Related Content PubMed PubMed Citation Articles by Hu, X. Articles by Fiering, S. Related Collections Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Deletion of the core region of 5' HS2 of the mouse -globin locus control region reveals a distinct effect in comparison with human -globin transgenes Xiao Hu, Michael Bulger, M. A. Bender, Jennifer Fields, Mark Groudine, and Steven Fiering From the Departments of Microbiology/Immunology and Genetics, Dartmouth Medical School, Hanover, NH; Center for Human Genetics and Molecular Pediatric Disease and Department of Biochemistry and Biophysics, University of Rochester, Rochester, NY; and Basic Science Division, Fred Hutchinson Cancer Research Center, Seattle WA. The -globin locus control region (LCR) is a large DNA element that is required for high-level expression of -like globin genes from the endogenous mouse locus or in transgenic mice carrying the human -globin locus. The LCR encompasses 6 DNaseI hypersensitive sites (HSs) that bind transcription factors. These HSs each contain a core of a few hundred base pairs (bp) that has most of the functional activity and exhibits high interspecies sequence homology. Adjoining the cores are 500- to 1000-bp "flanks" with weaker functional activity and lower interspecies homology. Studies of human -globin transgenes and of the endogenous murine locus show that deletion of an entire HS (core plus flanks) moderately suppresses expression. However, human transgenes in which only individual HS core regions were deleted showed drastic loss of expression accompanied by changes in chromatin structure. To address these disparate results, we have deleted the core region of 5'HS2 from the endogenous murine -LCR. The phenotype was similar to that of the larger 5'HS2 deletion, with no apparent disruption of chromatin structure. These results demonstrate that the greater severity of HS core deletions in comparison to full HS deletions is not a general property of the -LCR. (Blood. 2006;107:821-826) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Ross, S. Bottardi, V. Bourgoin, A. Wollenschlaeger, E. Drobetsky, M. Trudel, and E. Milot Differential requirement of a distal regulatory region for pre-initiation complex formation at globin gene promoters Nucleic Acids Res., September 1, 2009; 37(16): 5295 - 5308. [Abstract] [Full Text] [PDF] T. Chakraborty, T. Perlot, R. Subrahmanyam, A. Jani, P. H. Goff, Y. Zhang, I. Ivanova, F. W. Alt, and R. Sen A 220-nucleotide deletion of the intronic enhancer reveals an epigenetic hierarchy in immunoglobulin heavy chain locus activation J. Exp. Med., May 11, 2009; 206(5): 1019 - 1027. [Abstract] [Full Text] [PDF] M. A. Bender, R. Byron, T. Ragoczy, A. Telling, M. Bulger, and M. Groudine Flanking HS-62.5 and 3' HS1, and regions upstream of the LCR, are not required for beta-globin transcription Blood, August 15, 2006; 108(4): 1395 - 1401. [Abstract] [Full Text] [PDF]

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