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Tissue-specific histone modification and transcription factor binding in α globin gene expression

2007; Elsevier BV; Volume: 110; Issue: 13 Linguagem: Inglês

10.1182/blood-2007-06-097964

1528-0020

Marco De Gobbi, Eduardo Anguita, Jim R. Hughes, Jacqueline A. Sloane-Stanley, Jacqueline A. Sharpe, Christof Koch, Ian Dunham, Richard J. Gibbons, W. G. Wood, Douglas R. Higgs,

Cancer-related gene regulation

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 α globin genes and 9 widely expressed genes flanking the α 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 α 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.