title: Species-specific transcription in mice carrying human chromosome 21.
abstract: 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.
authors.affiliation: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wilson
authors.forename: Nuno L
authors.initials: NL
authors.lastname: Barbosa-Morais
authors.forename: Dominic
authors.initials: D
authors.lastname: Schmidt
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Conboy
authors.forename: Lesley
authors.initials: L
authors.lastname: Vanes
authors.forename: Victor L J
authors.initials: VL
authors.lastname: Tybulewicz
authors.forename: Elizabeth M C
authors.initials: EM
authors.lastname: Fisher
authors.forename: Simon
authors.initials: S
authors.lastname: Tavaré
authors.forename: Duncan T
authors.initials: DT
authors.lastname: Odom
mesh_terms: D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics; D005786:Gene Expression Regulation; D051536:Hepatocyte Nuclear Factors / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D012045:Regulatory Sequences, Nucleic Acid; D013045:Species Specificity; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D051536:Hepatocyte Nuclear Factors; D006657:Histones
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