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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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RED CELLS

Tissue-specific histone modification and transcription factor binding in {alpha} globin gene expression

Marco De Gobbi1, Eduardo Anguita1, Jim Hughes1, Jacqueline A. Sloane-Stanley1, Jacqueline A. Sharpe1, Christoph M. Koch2, Ian Dunham2, Richard J. Gibbons1, William G. Wood1, and Douglas R. Higgs1

1 Medical Research Council, Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, United Kingdom; and 2 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hixton, United Kingdom

To address the mechanism by which the human globin genes are activated during erythropoiesis, we have used a tiled microarray to analyze the pattern of transcription factor binding and associated histone modifications across the telomeric region of human chromosome 16 in primary erythroid and nonerythroid cells. This 220-kb region includes the {alpha} globin genes and 9 widely expressed genes flanking the {alpha} globin locus. This un-biased, 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 {alpha} globin cluster but also demonstrated that there are no additional erythroid-specific regulatory elements in the 220-kb 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 coexpressed in the same animal, showed significant differences that may explain how these 2 clusters are regulated differently in vivo.


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