SEARCH:   Advanced

Blood, 15 October 2009, Vol. 114, No. 16, pp. 3479-3488. Prepublished online as a Blood First Edition Paper on August 18, 2009; DOI 10.1182/blood-2009-03-210690. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: blood-2009-03-210690v1 114/16/3479    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 CrossRef Google Scholar Articles by Fromm, G. Articles by Bulger, M. PubMed PubMed Citation Articles by Fromm, G. Articles by Bulger, 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 Histone hyperacetylation within the β-globin locus is context-dependent and precedes high-level gene expression George Fromm1,2, Christina de Vries1, Rachel Byron3, Jennifer Fields4, Steven Fiering4, Mark Groudine3, M. A. Bender5, James Palis1, and Michael Bulger1,2 Departments of 1 Pediatrics and 2 Biochemistry and Biophysics, University of Rochester Medical Center, Center for Pediatric Biomedical Research, NY; 3 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; 4 Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH; and 5 Department of Pediatrics, University of Washington, Seattle Active gene promoters are associated with covalent histone modifications, such as hyperacetylation, which can modulate chromatin structure and stabilize binding of transcription factors that recognize these modifications. At the β-globin locus and several other loci, however, histone hyperacetylation extends beyond the promoter, over tens of kilobases; we term such patterns of histone modifications "hyperacetylated domains." Little is known of either the mechanism by which these domains form or their function. Here, we show that domain formation within the murine β-globin locus occurs before either high-level gene expression or erythroid commitment. Analysis of β-globin alleles harboring deletions of promoters or the locus control region demonstrates that these sequences are not required for domain formation, suggesting the existence of additional regulatory sequences within the locus. Deletion of embryonic globin gene promoters, however, resulted in the formation of a hyperacetylated domain over these genes in definitive erythroid cells, where they are otherwise inactive. Finally, sequences within β-globin domains exhibit hyperacetylation in a context-dependent manner, and domains are maintained when transcriptional elongation is inhibited. These data narrow the range of possible mechanisms by which hyperacetylated domains form. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020