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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.

Original publication

DOI

10.1182/blood-2007-06-097964

Type

Journal article

Journal

Blood

Publication Date

15/12/2007

Volume

110

Pages

4503 - 4510

Keywords

Acetylation, Animals, Cells, Cultured, Chromosomes, Human, Pair 16, Enhancer Elements, Genetic, Erythroblasts, Gene Expression Regulation, Globins, Histones, Humans, K562 Cells, Methylation, Mice, Promoter Regions, Genetic, T-Lymphocytes, Telomere, Transcription Factors, Transcription, Genetic