Journal
SCIENCE
Volume 322, Issue 5900, Pages 434-438Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1160930
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Funding
- European Research Council
- Royal Society Wolfson Research Merit Award
- Hutchison Whampoa
- Medical Research Council
- Wellcome Trust
- University of Cambridge
- Cancer Research U.K.
- MRC [G0601056, MC_U117527252] Funding Source: UKRI
- Medical Research Council [MC_U117527252, G0601056] Funding Source: researchfish
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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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