Species-specific transcription in mice carrying human chromosome 21

Science. 2008 Oct 17;322(5900):434-8. doi: 10.1126/science.1160930. Epub 2008 Sep 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Nucleus / metabolism
  • Chromatin Assembly and Disassembly
  • Chromatin Immunoprecipitation
  • Chromosomes, Human, Pair 21 / genetics*
  • Chromosomes, Human, Pair 21 / metabolism
  • Disease Models, Animal
  • Down Syndrome / genetics
  • Gene Expression Regulation*
  • Hepatocyte Nuclear Factors / metabolism*
  • Hepatocytes / metabolism*
  • Histones / metabolism
  • Humans
  • Methylation
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Regulatory Sequences, Nucleic Acid*
  • Species Specificity
  • Transcription Initiation Site
  • Transcription, Genetic*


  • Hepatocyte Nuclear Factors
  • Histones