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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1395-1401. Prepublished online as a Blood First Edition Paper on April 27, 2006; DOI 10.1182/blood-2006-04-014431. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-014431v1 108/4/1395    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 Bender, M. A. Articles by Groudine, M. Search for Related Content PubMed PubMed Citation Articles by Bender, M. A. Articles by Groudine, M. Related Collections Red Cells Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Flanking HS-62.5 and 3' HS1, and regions upstream of the LCR, are not required for -globin transcription M. A. Bender, Rachel Byron, Tobias Ragoczy, Agnes Telling, Michael Bulger, and Mark Groudine From the Divisions of Clinical Research and Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of Pediatrics and Radiation Oncology, University of Washington, Seattle, WA; and the Center for Pediatric Biomedical Research and Department of Biochemistry and Biophysics, University of Rochester, NY. The locus control region (LCR) was thought to be necessary and sufficient for establishing and maintaining an open -globin locus chromatin domain in the repressive environment of the developing erythrocyte. However, deletion of the LCR from the endogenous locus had no significant effect on chromatin structure and did not silence transcription. Thus, the cis-regulatory elements that confer the open domain remain unidentified. The conserved DNaseI hypersensitivity sites (HSs) HS-62.5 and 3'HS1 that flank the locus, and the region upstream of the LCR have been implicated in globin gene regulation. The flanking HSs bind CCCTC binding factor (CTCF) and are thought to interact with the LCR to form a "chromatin hub" involved in -globin gene activation. Hispanic thalassemia, a deletion of the LCR and 27 kb upstream, leads to heterochromatinization and silencing of the locus. Thus, the region upstream of the LCR deleted in Hispanic thalassemia (upstream Hispanic region [UHR]) may be required for expression. To determine the importance of the UHR and flanking HSs for -globin expression, we generated and analyzed mice with targeted deletions of these elements. We demonstrate deletion of these regions alone, and in combination, do not affect transcription, bringing into question current models for the regulation of the -globin locus. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A lack of border guards? William G. Wood and Douglas R. Higgs Blood 2006 108: 1121. [Full Text] [PDF] This article has been cited by other articles: R.-J. T. S. Palstra Close encounters of the 3C kind: long-range chromatin interactions and transcriptional regulation Brief Funct Genomic Proteomic, July 27, 2009; (2009) elp016v2. [Abstract] [Full Text] [PDF] V. Singh and M. Srivastava Enhancer Blocking Activity of the Insulator at H19-ICR Is Independent of Chromatin Barrier Establishment Mol. Cell. Biol., June 1, 2008; 28(11): 3767 - 3775. [Abstract] [Full Text] [PDF] J. Kooren, R.-J. Palstra, P. Klous, E. Splinter, M. von Lindern, F. Grosveld, and W. de Laat beta-Globin Active Chromatin Hub Formation in Differentiating Erythroid Cells and in p45 NF-E2 Knock-out Mice J. Biol. Chem., June 1, 2007; 282(22): 16544 - 16552. [Abstract] [Full Text] [PDF] A. Kim, C. M. Kiefer, and A. Dean Distinctive Signatures of Histone Methylation in Transcribed Coding and Noncoding Human {beta}-Globin Sequences Mol. Cell. Biol., February 15, 2007; 27(4): 1271 - 1279. [Abstract] [Full Text] [PDF] J. Dostie, T. A. Richmond, R. A. Arnaout, R. R. Selzer, W. L. Lee, T. A. Honan, E. D. Rubio, A. Krumm, J. Lamb, C. Nusbaum, et al. Chromosome Conformation Capture Carbon Copy (5C): A massively parallel solution for mapping interactions between genomic elements Genome Res., October 1, 2006; 16(10): 1299 - 1309. [Abstract] [Full Text] [PDF]

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