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

Nat Genet. 2007 Jun;39(6):730-2. doi: 10.1038/ng2047. Epub 2007 May 21.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conserved Sequence / genetics*
  • Gene Expression Regulation*
  • Genetic Variation
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Hepatocyte Nuclear Factor 3-beta / genetics
  • Hepatocyte Nuclear Factor 4 / genetics
  • Hepatocyte Nuclear Factor 6 / genetics
  • Humans
  • Mice
  • Regulatory Sequences, Nucleic Acid*
  • Sequence Homology
  • Transcription Factors / genetics*
  • Transcription, Genetic*


  • FOXA2 protein, human
  • Foxa2 protein, mouse
  • HNF1A protein, human
  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 4
  • Hepatocyte Nuclear Factor 6
  • Hnf1a protein, mouse
  • Hnf4a protein, mouse
  • Transcription Factors
  • Hepatocyte Nuclear Factor 3-beta