title: Tissue-specific histone modification and transcription factor binding in alpha globin gene expression.
abstract: 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.
authors: Medical Research Council, Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
authors: Marco
authors: M
authors: De Gobbi
authors: Eduardo
authors: E
authors: Anguita
authors: Jim
authors: J
authors: Hughes
authors: Jacqueline A
authors: JA
authors: Sloane-Stanley
authors: Jacqueline A
authors: JA
authors: Sharpe
authors: Christoph M
authors: CM
authors: Koch
authors: Ian
authors: I
authors: Dunham
authors: Richard J
authors: RJ
authors: Gibbons
authors: William G
authors: WG
authors: Wood
authors: Douglas R
authors: DR
authors: Higgs
mesh_terms: D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D002885:Chromosomes, Human, Pair 16; D004742:Enhancer Elements, Genetic; D004900:Erythroblasts / Q000276:immunology; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D008745:Methylation; D051379:Mice; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000166:cytology; D016615:Telomere; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D006657:Histones; D014157:Transcription Factors; D005914:Globins