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Originally published in Science Express on 11 September 2008
Science 17 October 2008:
Vol. 322. no. 5900, pp. 434 - 438
DOI: 10.1126/science.1160930
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Reports

Species-Specific Transcription in Mice Carrying Human Chromosome 21

Michael D. Wilson,1* Nuno L. Barbosa-Morais,1,2* Dominic Schmidt,1,2 Caitlin M. Conboy,3 Lesley Vanes,4 Victor L. J. Tybulewicz,4 Elizabeth M. C. Fisher,5 Simon Tavaré,1,2,6 Duncan T. Odom1,2{dagger}

Homologous sets of transcription factors direct conserved tissue-specific gene expression, yet transcription factor–binding 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–binding 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.

1 Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
2 Department of Oncology, Hutchison/MRC (Medical Research Council) Research Centre, Hills Road, Cambridge CB2 0XZ, UK.
3 Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
4 Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
5 Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
6 Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB3 0WA, UK.

* These authors contributed equally to this work

{dagger} To whom correspondence should be addressed. E-mail: duncan.odom{at}cancer.org.uk

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