{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T02:06:47Z","timestamp":1773713207213,"version":"3.50.1"},"reference-count":26,"publisher":"Proceedings of the National Academy of Sciences","issue":"51","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,12,22]]},"abstract":"<jats:p>\n                    It is well established that all of the\n                    <jats:italic>cis<\/jats:italic>\n                    -acting sequences required for fully regulated human \u03b1-globin expression are contained within a region of \u2248120 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 (\n                    <jats:italic>NME4<\/jats:italic>\n                    ) located 300 kb from the \u03b1-globin cluster. Changes in\n                    <jats:italic>NME4<\/jats:italic>\n                    expression are mediated by physical\n                    <jats:italic>cis<\/jats:italic>\n                    -interactions between this gene and the \u03b1-globin regulatory elements. Polymorphic structural variation within the globin cluster, altering the number of \u03b1-globin genes, affects the pattern of\n                    <jats:italic>NME4<\/jats:italic>\n                    expression by altering the competition for the shared \u03b1-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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0909331106","type":"journal-article","created":{"date-parts":[[2009,12,3]],"date-time":"2009-12-03T22:43:31Z","timestamp":1259880211000},"page":"21771-21776","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":81,"title":["Adventitious changes in long-range gene expression caused by polymorphic structural variation and promoter competition"],"prefix":"10.1073","volume":"106","author":[{"given":"Karen M.","family":"Lower","sequence":"first","affiliation":[{"name":"Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford, OX3 9DS, United Kingdom;"}]},{"given":"Jim R.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford, OX3 9DS, United Kingdom;"}]},{"given":"Marco","family":"De Gobbi","sequence":"additional","affiliation":[{"name":"Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford, OX3 9DS, United Kingdom;"}]},{"given":"Shirley","family":"Henderson","sequence":"additional","affiliation":[{"name":"National Haemoglobinopathy Reference Laboratory, Oxford Radcliffe Hospitals NHS Trust, Oxford, OX3 7LJ, United Kingdom;"}]},{"given":"Vip","family":"Viprakasit","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Faculty of Medicine, Siriaj Hospital, Mahidol University, Bangkok, 10700, Thailand; and"}]},{"given":"Chris","family":"Fisher","sequence":"additional","affiliation":[{"name":"Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford, OX3 9DS, United Kingdom;"}]},{"given":"Anne","family":"Goriely","sequence":"additional","affiliation":[{"name":"Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford, OX3 9DS, United Kingdom;"}]},{"given":"Helena","family":"Ayyub","sequence":"additional","affiliation":[{"name":"Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford, OX3 9DS, United Kingdom;"}]},{"given":"Jackie","family":"Sloane-Stanley","sequence":"additional","affiliation":[{"name":"Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford, OX3 9DS, United Kingdom;"}]},{"given":"Douglas","family":"Vernimmen","sequence":"additional","affiliation":[{"name":"Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford, OX3 9DS, United Kingdom;"}]},{"given":"Cordelia","family":"Langford","sequence":"additional","affiliation":[{"name":"Microarray Facility, The Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, United Kingdom"}]},{"given":"David","family":"Garrick","sequence":"additional","affiliation":[{"name":"Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford, OX3 9DS, United Kingdom;"}]},{"given":"Richard J.","family":"Gibbons","sequence":"additional","affiliation":[{"name":"Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford, OX3 9DS, United Kingdom;"}]},{"given":"Douglas R.","family":"Higgs","sequence":"additional","affiliation":[{"name":"Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford, OX3 9DS, United Kingdom;"}]}],"member":"341","published-online":{"date-parts":[[2009,12,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.12.048"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/426833"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2005.11.001"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503401102"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-097964"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.11.044"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.19.14264"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050405"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0b013e3282f734c4"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2009.06.004"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601654"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-213439"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1891"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1896"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.397"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-014431"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600365"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1024922626726"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90005-0"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80014-3"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V73.5.1081.1081"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1126431"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00310-6"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1136678"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0609.2000.90032.x"},{"key":"e_1_3_3_26_2","first-page":"328","article-title":"The removal of leukocytes and platelets from whole blood","volume":"88","author":"Beutler E","year":"1976","unstructured":"E Beutler, C West, KG Blume, The removal of leukocytes and platelets from whole blood. 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