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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3889-3899. Prepublished online as a Blood First Edition Paper on August 8, 2008; DOI 10.1182/blood-2008-06-161901. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-06-161901v1 112/9/3889    most recent Alert me when this article is cited Alert me if a correction is posted 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 Garrick, D. Articles by Higgs, D. R Search for Related Content PubMed PubMed Citation Articles by Garrick, D. Articles by Higgs, D. R Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 9, 2008 Accepted July 21, 2008 The role of the polycomb complex in silencing -globin gene expression in non-erythroid cells David Garrick, Marco De Gobbi, Vasiliki Samara, Michelle Rugless, Michelle Holland, Helena Ayyub, Karen Lower, Jackie Sloane-Stanley, Nicki Gray, Christoph Koch, Ian Dunham, and Douglas R Higgs* MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom European Bioinformatics Institute (EBI), Wellcome Trust Genome Campus, Cambridge, United Kingdom * Corresponding author; email: doug.higgs{at}imm.ox.ac.uk. Although much is known about globin gene activation in erythroid cells, relatively little is known about how these genes are silenced in non-erythroid tissues. Here we show that the human - and -gobin genes are silenced by fundamentally different mechanisms. The -genes, which are surrounded by widely expressed genes in a gene dense region of the genome, are silenced very early in development via recruitment of the Polycomb (PcG) complex. By contrast, the -globin genes, which lie in a relatively gene poor chromosomal region are not bound by this complex in non-erythroid cells. The PcG complex appears to be recruited to the -cluster by sequences within the CpG islands associated with their promoters: the -globin promoters do not lie within such islands. Chromatin associated with the -globin cluster is modified by histone methylation (H3K27me3) and silencing in vivo is mediated by the localised activity of histone deacetylases (HDACs). The repressive (PcG/HDAC) machinery is removed as hematopoietic progenitors differentiate to form erythroid cells. The - and -globin genes thus illustrate important, contrasting mechanisms by which cell-specific hematopoietic genes (and tissue-specific genes in general) may be silenced. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. M. Pauler, M. A. Sloane, R. Huang, K. Regha, M. V. Koerner, I. Tamir, A. Sommer, A. Aszodi, T. Jenuwein, and D. P. Barlow H3K27me3 forms BLOCs over silent genes and intergenic regions and specifies a histone banding pattern on a mouse autosomal chromosome Genome Res., February 1, 2009; 19(2): 221 - 233. [Abstract] [Full Text] [PDF]

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