Brief Communication abstract


Nature Genetics 39, 730 - 732 (2007)
Published online: 21 May 2007 | doi:10.1038/ng2047

Tissue-specific transcriptional regulation has diverged significantly between human and mouse

Duncan T Odom1,5,6, Robin D Dowell2,6, Elizabeth S Jacobsen1, William Gordon3, Timothy W Danford2, Kenzie D MacIsaac4, P Alexander Rolfe2, Caitlin M Conboy1,5, David K Gifford1,2 & Ernest Fraenkel2,3

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We demonstrate that the binding sites for highly conserved transcription factors vary extensively between human and mouse. We mapped the binding of four tissue-specific transcription factors (FOXA2, HNF1A, HNF4A and HNF6) to 4,000 orthologous gene pairs in hepatocytes purified from human and mouse livers. Despite the conserved function of these factors, from 41% to 89% of their binding events seem to be species specific. When the same protein binds the promoters of orthologous genes, approximately two-thirds of the binding sites do not align.

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  1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
  2. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
  3. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
  4. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
  5. Present address: Cancer Research UK–Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
  6. These authors contributed equally to this work.

Correspondence to: Ernest Fraenkel2,3 e-mail: fraenkel-admin@mit.edu

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