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

Nature Genetics volume 39, pages 730–732 (2007) Cite this article

Abstract

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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Figure 1: Strategy to analyze interactions between transcription factors and DNA in mouse and human.
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Figure 2: Comparison of binding in human and mouse.
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Acknowledgements

We are grateful to S. Strom and K. Dorko (University of Pittsburgh) for human liver samples (DK92310); T. DiCesare, S. Gupta, R. Kumar, J. Rodriguez and K. Walker for technical assistance and R. Young and G. Gerber for discussions. This work was supported by funding from US National Institutes of Health (grants DK68655 and DK70813 (D.T.O.) and DK076284 (R.D.D.)), Cancer Research UK (D.T.O.) and the Whitaker Foundation (E.F.).

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Author notes

  1. Duncan T Odom & Caitlin M Conboy

    Present address: Present address: Cancer Research UK–Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.,

  2. Duncan T Odom and Robin D Dowell: These authors contributed equally to this work.

Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, 02142, Massachusetts, USA

    Duncan T Odom, Elizabeth S Jacobsen, Caitlin M Conboy & David K Gifford

  2. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Robin D Dowell, Timothy W Danford, P Alexander Rolfe, David K Gifford & Ernest Fraenkel

  3. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    William Gordon & Ernest Fraenkel

  4. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Kenzie D MacIsaac

Authors
  1. Duncan T Odom
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  2. Robin D Dowell
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Contributions

D.T.O., R.D.D. and E.F. designed experiments; R.D.D. designed the arrays; D.T.O., E.S.J., W.G. and C.M.C. performed experiments; R.D.D., T.W.D, K.D.M., P.A.R. and E.F. analyzed the data and D.T.O, R.D.D., D.K.G. and E.F. created the manuscript.

Corresponding author

Correspondence to Ernest Fraenkel.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1 (download PDF )

Binding to known liver-specific genes. (PDF 198 kb)

Supplementary Fig. 2 (download PDF )

Species-specific binding does not arise from technical limitations. (PDF 369 kb)

Supplementary Fig. 3 (download PDF )

Distance from binding maxima to motif sequences. (PDF 109 kb)

Supplementary Table 1 (download PDF )

Conservation of transcription factors and expression in human and mouse liver. (PDF 88 kb)

Supplementary Table 2 (download PDF )

Species-specific binding does not arise from technical limitations. (PDF 266 kb)

Supplementary Table 3 (download PDF )

Analysis of motif sequences and alignments. (PDF 583 kb)

Supplementary Methods (PDF 27 kb) (download PDF )

Supplementary Note (PDF 53 kb) (download PDF )

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Odom, D., Dowell, R., Jacobsen, E. et al. Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat Genet 39, 730–732 (2007). https://doi.org/10.1038/ng2047

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