TY - JOUR
T1 - Species-specific transcription in mice carrying human chromosome 21
AU - Wilson, Michael D.
AU - Barbosa-Morais, Nuno L.
AU - Schmidt, Dominic
AU - Conboy, Caitlin M.
AU - Vanes, Lesley
AU - Tybulewicz, Victor L.J.
AU - Fisher, Elizabeth M.C.
AU - Tavaré, Simon
AU - Odom, Duncan T.
PY - 2008/10/17
Y1 - 2008/10/17
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1160930
DO - 10.1126/science.1160930
M3 - Article
C2 - 18787134
AN - SCOPUS:54249099196
SN - 0036-8075
VL - 322
SP - 434
EP - 438
JO - Science
JF - Science
IS - 5900
ER -