{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T08:48:09Z","timestamp":1777106889554,"version":"3.51.4"},"reference-count":31,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5900","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2008,10,17]]},"abstract":"<jats:p>Homologous sets of transcription factors direct conserved tissue-specific gene expression, yet transcription factor\u2013binding events diverge rapidly between closely related species. We used hepatocytes from an aneuploid mouse strain carrying human chromosome 21 to determine, on a chromosomal scale, whether interspecies differences in transcriptional regulation are primarily directed by human genetic sequence or mouse nuclear environment. Virtually all transcription factor\u2013binding locations, landmarks of transcription initiation, and the resulting gene expression observed in human hepatocytes were recapitulated across the entire human chromosome 21 in the mouse hepatocyte nucleus. Thus, in homologous tissues, genetic sequence is largely responsible for directing transcriptional programs; interspecies differences in epigenetic machinery, cellular environment, and transcription factors themselves play secondary roles.<\/jats:p>","DOI":"10.1126\/science.1160930","type":"journal-article","created":{"date-parts":[[2008,9,11]],"date-time":"2008-09-11T21:10:11Z","timestamp":1221167411000},"page":"434-438","source":"Crossref","is-referenced-by-count":258,"title":["Species-Specific Transcription in Mice Carrying Human Chromosome 21"],"prefix":"10.1126","volume":"322","author":[{"given":"Michael D.","family":"Wilson","sequence":"first","affiliation":[{"name":"Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK."},{"name":"Department of Oncology, Hutchison\/MRC (Medical Research Council) Research Centre, Hills Road, Cambridge CB2 0XZ, UK."},{"name":"Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK."},{"name":"Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}]},{"given":"Nuno L.","family":"Barbosa-Morais","sequence":"additional","affiliation":[{"name":"Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK."},{"name":"Department of Oncology, Hutchison\/MRC (Medical Research Council) Research Centre, Hills Road, Cambridge CB2 0XZ, UK."},{"name":"Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK."},{"name":"Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}]},{"given":"Dominic","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK."},{"name":"Department of Oncology, Hutchison\/MRC (Medical Research Council) Research Centre, Hills Road, Cambridge CB2 0XZ, UK."},{"name":"Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK."},{"name":"Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}]},{"given":"Caitlin M.","family":"Conboy","sequence":"additional","affiliation":[{"name":"Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK."},{"name":"Department of Oncology, Hutchison\/MRC (Medical Research Council) Research Centre, Hills Road, Cambridge CB2 0XZ, UK."},{"name":"Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK."},{"name":"Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}]},{"given":"Lesley","family":"Vanes","sequence":"additional","affiliation":[{"name":"Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK."},{"name":"Department of Oncology, Hutchison\/MRC (Medical Research Council) Research Centre, Hills Road, Cambridge CB2 0XZ, UK."},{"name":"Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK."},{"name":"Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}]},{"given":"Victor L. J.","family":"Tybulewicz","sequence":"additional","affiliation":[{"name":"Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK."},{"name":"Department of Oncology, Hutchison\/MRC (Medical Research Council) Research Centre, Hills Road, Cambridge CB2 0XZ, UK."},{"name":"Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK."},{"name":"Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}]},{"given":"Elizabeth M. C.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK."},{"name":"Department of Oncology, Hutchison\/MRC (Medical Research Council) Research Centre, Hills Road, Cambridge CB2 0XZ, UK."},{"name":"Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK."},{"name":"Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}]},{"given":"Simon","family":"Tavare\u0301","sequence":"additional","affiliation":[{"name":"Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK."},{"name":"Department of Oncology, Hutchison\/MRC (Medical Research Council) Research Centre, Hills Road, Cambridge CB2 0XZ, UK."},{"name":"Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK."},{"name":"Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}]},{"given":"Duncan T.","family":"Odom","sequence":"additional","affiliation":[{"name":"Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK."},{"name":"Department of Oncology, Hutchison\/MRC (Medical Research Council) Research Centre, Hills Road, Cambridge CB2 0XZ, UK."},{"name":"Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN 55455, USA."},{"name":"Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK."},{"name":"Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK."}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1113832"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(99)00326-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2063"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.01.015"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1434"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.4140006"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng2047"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0020130"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1140748"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05874"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.01.001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1558-5646.2007.00105.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.030"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1114535"},{"key":"e_1_3_2_16_2","unstructured":"Materials and methods are available as supporting material on Science Online."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.2094104"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.05.008"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.10.2.8641560"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg850"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.10.6509"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi378"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.042"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.08.016"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.11.010"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.009"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04559"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1108296"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.77"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.113"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2008.06.001"},{"key":"e_1_3_2_32_2","unstructured":"We are grateful to E. Jacobsen R. Stark I. Spiteri B. Liu J. Marioni A. Lynch J. Hadfield N. Matthews the Cambridge Research Institute (CRI) Genomics Core CRI Bioinformatics Core and Camgrid for technical assistance and B. Gottgens and J. Ferrer for insightful advice. Supported by the European Research Council (D.T.O.); Royal Society Wolfson Research Merit Award (S.T.); Hutchison Whampoa (D.T.O. ST); Medical Research Council (E.F. VT); Wellcome Trust (E.F. V.T.); University of Cambridge (D.T.O. D.S. N.B.M. S.T.); and Cancer Research U.K. (D.T.O. M.D.W. N.B.M. S.T. D.S.). Data deposited under ArrayExpress accession numbers E-TABM-473 and E-TABM-474. M.D.W. N.B.M. D.S. D.T.O. and C.M.C. designed and performed experiments; N.B.M. M.D.W. and D.S. analyzed the data; L.V. V.T. M.D.W. and E.F. created prepared and provided Tc1 mouse tissues; and M.D.W. N.B.M. D.T.O. and S.T. wrote the manuscript. D.T.O. oversaw the work. The authors declare no competing interests."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1160930","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T02:57:20Z","timestamp":1704855440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1160930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,17]]},"references-count":31,"journal-issue":{"issue":"5900","published-print":{"date-parts":[[2008,10,17]]}},"alternative-id":["10.1126\/science.1160930"],"URL":"https:\/\/doi.org\/10.1126\/science.1160930","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1123190.581510","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1123190.580324","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1123190.595925","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1123190.583929","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1123190.584269","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1123190.581420","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1123190.2742062","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1123190.583861","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,17]]}}}