Divergence of nucleosome positioning between two closely related yeast species: genetic basis and functional consequences.
Gene regulation differs greatly between related species, constituting a major source of phenotypic diversity. Recent studies characterized extensive differences in the gene expression programs of closely related species. In contrast, virtually nothing is known about the evolution of chromatin structure and how it influences the divergence of gene expression. Here, we compare the genome-wide nucleosome positioning of two closely related yeast species and, by profiling their inter-specific hybrid, trace the genetic basis of the observed differences into mutations affecting the local DNA sequences (cis effects) or the upstream regulators (trans effects). The majority (approximately 70%) of inter-species differences is due to cis effects, leaving a significant contribution (30%) for trans factors. We show that cis effects are well explained by mutations in nucleosome-disfavoring AT-rich sequences, but are not associated with divergence of nucleosome-favoring sequences. Differences in nucleosome positioning propagate to multiple adjacent nucleosomes, supporting the statistical positioning hypothesis, and we provide evidence that nucleosome-free regions, but not the +1 nucleosome, serve as stable border elements. Surprisingly, although we find that differential nucleosome positioning among cell types is strongly correlated with differential expression, this does not seem to be the case for evolutionary changes: divergence of nucleosome positioning is excluded from regulatory elements and is not correlated with gene expression divergence, suggesting a primarily neutral mode of evolution. Our results provide evolutionary insights to the genetic determinants and regulatory function of nucleosome positioning.
Tirosh
Itay
I
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Sigal
Nadejda
N
Barkai
Naama
N
D020856:AT Rich Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics*; D002678:Chimera / Q000235:genetics*; D019295:Computational Biology; D019143:Evolution, Molecular; D015966:Gene Expression Regulation, Fungal; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*
D009707:Nucleosomes
Cell. 2007 Feb 23;128(4):707-19
17320508
Nat Struct Mol Biol. 2010 Feb;17(2):251-7
20118936
BMC Bioinformatics. 2006 Mar 07;7:113
16522208
Nat Rev Genet. 2007 Mar;8(3):206-16
17304246
Nat Rev Genet. 2006 Sep;7(9):693-702
16921347
Nat Genet. 2007 Oct;39(10):1235-44
17873876
Nat Genet. 2003 Feb;33(2):138-44
12548287
Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14062-7
16968785
Genome Res. 2010 Jan;20(1):90-100
19846608
PLoS Comput Biol. 2007 May;3(5):e99
17530920
Trends Genet. 2004 Sep;20(9):403-7
15313547
Science. 2009 May 1;324(5927):659-62
19407207
Nature. 2006 Aug 17;442(7104):772-8
16862119
Mol Syst Biol. 2008;4:159
18197176
Science. 2007 Aug 10;317(5839):815-9
17690298
Nat Genet. 2009 Apr;41(4):438-45
19252487
Genome Res. 2010 Mar;20(3):361-71
20086243
Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18069-74
15604142
Science. 1975 Apr 11;188(4184):107-16
1090005
Nat Genet. 2008 Feb;40(2):141-7
18227874
Nature. 2003 May 15;423(6937):241-54
12748633
Mol Biol Cell. 2009 Aug;20(15):3503-13
19494041
Nat Genet. 2004 Aug;36(8):900-5
15247917
Science. 2005 Jul 22;309(5734):626-30
15961632
Science. 2005 Aug 5;309(5736):938-40
16081737
Nature. 2004 Jul 1;430(6995):85-8
15229602
Nat Genet. 2007 Jun;39(6):730-2
17529977
EMBO J. 1995 Jun 1;14(11):2570-9
7781610
Nat Struct Mol Biol. 2009 Aug;16(8):847-52
19620965
Nature. 2007 Dec 13;450(7172):1031-5
18075583
PLoS Genet. 2006 Sep 22;2(9):e158
17002501
Curr Opin Struct Biol. 2009 Feb;19(1):65-71
19208466
Nat Genet. 2006 Oct;38(10):1210-5
16964265
PLoS Biol. 2008 Mar 18;6(3):e65
18351804
Mol Cell. 2008 Dec 26;32(6):878-87
19111667
PLoS Comput Biol. 2008 Nov;4(11):e1000216
18989395
Nature. 2009 Mar 19;458(7236):362-6
19092803
PLoS Biol. 2005 Oct;3(10):e328
16122352
Nat Biotechnol. 2007 Feb;25(2):244-8
17220878
Cell. 2005 Aug 26;122(4):517-27
16122420
Nucleic Acids Res. 1988 Jul 25;16(14A):6677-90
3399412
Genome Res. 2008 Jul;18(7):1073-83
18550805
Cell. 2009 May 1;137(3):445-58
19410542