Tissue-specific histone modification and transcription factor binding in alpha globin gene expression.
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.
De Gobbi
Marco
M
Medical Research Council, Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
Anguita
Eduardo
E
Hughes
Jim
J
Sloane-Stanley
Jacqueline A
JA
Sharpe
Jacqueline A
JA
Koch
Christoph M
CM
Dunham
Ian
I
Gibbons
Richard J
RJ
Wood
William G
WG
Higgs
Douglas R
DR
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*
D006657:Histones; D014157:Transcription Factors; D005914:Globins