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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4503-4510.
Prepublished online as a Blood First Edition Paper on August 22, 2007; DOI 10.1182/blood-2007-06-097964.
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Submitted June 26, 2007
Accepted August 20, 2007
Tissue-specific histone modification and transcription factor binding in  globin gene expression
Marco De Gobbi, Eduardo Anguita, Jim Hughes, Jacqueline A Sloane-Stanley, Jacqueline A Sharpe, Christoph M Koch, Ian Dunham, Richard J Gibbons, William G Wood, and Douglas R Higgs*
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, United Kingdom
Molecular Genetics and Proteomics, The Wellcome Trust Sanger Institute, Hixton, United Kingdom
* Corresponding author; email: doug.higgs{at}imm.ox.ac.uk.
To address the mechanism by which the human globin genes are activated during erythropoiesis, we have used a tiled microarray to analyse the pattern of transcription factor binding and associated histone modifications across the telomeric region of human chromosome 16 in primary erythroid and non-erythroid cells. This 220kb region includes the  globin genes and nine widely expressed genes flanking the globin locus. This unbiased, comprehensive analysis of transcription factor binding and histone modifications (acetylation and methylation) described here not only identified all known cis-acting regulatory elements in the human globin cluster but also demonstrated that there are no additional erythroid-specific regulatory elements in the 220kb region tested. In addition, the pattern of histone modification distinguished promoter elements from potential enhancer elements across this region. Finally, comparison of the human and mouse orthologous regions in a unique mouse model, with both regions co-expressed in the same animal, showed significant differences that may explain how these two clusters are regulated differently in vivo.
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