Species-specific transcription in mice carrying human chromosome 21.
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.
Wilson
Michael D
MD
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Barbosa-Morais
Nuno L
NL
Schmidt
Dominic
D
Conboy
Caitlin M
CM
Vanes
Lesley
L
Tybulewicz
Victor L J
VL
Fisher
Elizabeth M C
EM
Tavaré
Simon
S
Odom
Duncan T
DT
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
D051536:Hepatocyte Nuclear Factors; D006657:Histones
Science. 2007 Aug 10;317(5839):815-9
17690298
Evolution. 2007 May;61(5):995-1016
17492956
Nat Rev Genet. 2007 Mar;8(3):206-16
17304246
FASEB J. 1996 Feb;10(2):267-82
8641560
Genome Res. 2004 Mar;14(3):331-42
14993201
Nat Genet. 2008 Apr;40(4):421-9
18362883
Hum Mol Genet. 2005 Nov 15;14(22):3435-47
16221759
Cell. 2007 Jul 13;130(1):77-88
17632057
Nat Genet. 2007 Jun;39(6):730-2
17529977
Mol Cell Biol. 1999 Oct;19(10):6509-22
10490591
Mech Dev. 2000 Mar 15;92(1):83-8
10704889
Nature. 2006 Mar 9;440(7081):242-5
16525476
Cell. 2007 Feb 23;128(4):707-19
17320508
Genome Res. 2006 Dec;16(12):1455-64
17053094
Cell. 2007 May 18;129(4):823-37
17512414
Science. 2005 Sep 16;309(5742):1850-4
16141373
Trends Genet. 2008 Aug;24(8):408-15
18597885
PLoS Comput Biol. 2006 Oct;2(10):e130
17040121
Nat Genet. 2008 Mar;40(3):346-50
18278046
Nucleic Acids Res. 2003 Nov 15;31(22):6640-50
14602925
Cell. 2005 Jan 28;120(2):169-81
15680324
Mol Cell. 2007 Nov 30;28(4):665-76
18042460
Science. 2006 Feb 10;311(5762):796-800
16469913
Nat Cell Biol. 2006 Jul;8(7):764-70
16767079
Cell. 2008 Jul 11;134(1):25-36
18614008