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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/28379
Title: Adventitious changes in long-range gene expression caused by polymorphic structural variation and promoter competition
Authors: Karen M. Lower
Jim R. Hughes
Marco De Gobbi
Shirley Henderson
Vip Viprakasit
Chris Fisher
Anne Goriely
Helena Ayyub
Jackie Sloane-Stanley
Douglas Vernimmen
Cordelia Langford
David Garrick
Richard J. Gibbons
Douglas R. Higgs
John Radcliffe Hospital
Oxford Radcliffe Hospitals NHS Trust
Mahidol University
Wellcome Trust Sanger Institute
Keywords: Multidisciplinary
Issue Date: 22-Dec-2009
Citation: Proceedings of the National Academy of Sciences of the United States of America. Vol.106, No.51 (2009), 21771-21776
Abstract: It is well established that all of the cis-acting sequences required for fully regulated human α-globin expression are contained within a region of ≈120 kb of conserved synteny. Here, we show that activation of this cluster in erythroid cells dramatically affects expression of apparently unrelated and noncontiguous genes in the 500 kb surrounding this domain, including a gene (NME4) located 300 kb from the α-globin cluster. Changes in NME4 expression are mediated by physical cis-interactions between this gene and the α-globin regulatory elements. Polymorphic structural variation within the globin cluster, altering the number of α-globin genes, affects the pattern of NME4 expression by altering the competition for the shared α-globin regulatory elements. These findings challenge the concept that the genome is organized into discrete, insulated regulatory domains. In addition, this work has important implications for our understanding of genome evolution, the interpretation of genome-wide expression, expression-quantitative trait loci, and copy number variant analyses.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=76049106672&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/28379
ISSN: 10916490
00278424
Appears in Collections:Scopus 2006-2010

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