Quantitative test of the barrier nucleosome model for statistical positioning of nucleosomes up- and downstream of transcription start sites.
The positions of nucleosomes in eukaryotic genomes determine which parts of the DNA sequence are readily accessible for regulatory proteins and which are not. Genome-wide maps of nucleosome positions have revealed a salient pattern around transcription start sites, involving a nucleosome-free region (NFR) flanked by a pronounced periodic pattern in the average nucleosome density. While the periodic pattern clearly reflects well-positioned nucleosomes, the positioning mechanism is less clear. A recent experimental study by Mavrich et al. argued that the pattern observed in Saccharomyces cerevisiae is qualitatively consistent with a "barrier nucleosome model," in which the oscillatory pattern is created by the statistical positioning mechanism of Kornberg and Stryer. On the other hand, there is clear evidence for intrinsic sequence preferences of nucleosomes, and it is unclear to what extent these sequence preferences affect the observed pattern. To test the barrier nucleosome model, we quantitatively analyze yeast nucleosome positioning data both up- and downstream from NFRs. Our analysis is based on the Tonks model of statistical physics which quantifies the interplay between the excluded-volume interaction of nucleosomes and their positional entropy. We find that although the typical patterns on the two sides of the NFR are different, they are both quantitatively described by the same physical model with the same parameters, but different boundary conditions. The inferred boundary conditions suggest that the first nucleosome downstream from the NFR (the +1 nucleosome) is typically directly positioned while the first nucleosome upstream is statistically positioned via a nucleosome-repelling DNA region. These boundary conditions, which can be locally encoded into the genome sequence, significantly shape the statistical distribution of nucleosomes over a range of up to approximately 1,000 bp to each side.
Möbius
Wolfram
W
Arnold Sommerfeld Center for Theoretical Physics and Center for NanoScience, Ludwig-Maximilians Universität München, Munich, Germany.
Gerland
Ulrich
U
D001483:Base Sequence; D016681:Genome, Fungal; D038101:Insulator Elements / Q000235:genetics; D008954:Models, Biological; D015233:Models, Statistical; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000235:genetics*
D009707:Nucleosomes; D014157:Transcription Factors
Biopolymers. 2003 Apr;68(4):563-78
12666181
Nat Struct Mol Biol. 2006 Jul;13(7):633-40
16819518
Mol Biol Cell. 2009 Aug;20(15):3503-13
19494041
Q Rev Biophys. 2001 Aug;34(3):269-324
11838235
Phys Rev Lett. 2008 Jun 6;100(22):228105
18643465
Nat Struct Mol Biol. 2009 Aug;16(8):847-52
19620965
Nature. 1981 Aug 13;292(5824):579-80
7254354
Nature. 2007 Dec 13;450(7172):1031-5
18075583
Curr Opin Struct Biol. 2009 Feb;19(1):65-71
19208466
Science. 2009 Jan 16;323(5912):401-4
19074313
Phys Rev Lett. 2007 Nov 23;99(21):218103
18233262
PLoS Comput Biol. 2008 Jan;4(1):e13
18225943
J Mol Biol. 2009 Mar 13;386(5):1411-22
19070622
Nature. 2007 Mar 29;446(7135):572-6
17392789
Phys Rev Lett. 2009 Oct 30;103(18):188103
19905836
Nucleic Acids Res. 1981 Jun 25;9(12):2643-58
7279658
J Mol Biol. 1988 Nov 5;204(1):109-27
3063825
Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22257-62
20018700
Dev Biol. 2010 Mar 15;339(2):258-66
19527704
Annu Rev Biochem. 2009;78:273-304
19355820
Nat Genet. 2007 Oct;39(10):1235-44
17873876
Science. 2005 Jul 22;309(5734):626-30
15961632
Nat Struct Mol Biol. 2005 Jan;12(1):46-53
15580276
Phys Rev Lett. 2006 Nov 17;97(20):208102
17155720
J Mol Biol. 2002 Jun 21;319(5):1097-113
12079350
PLoS Biol. 2008 Mar 18;6(3):e65
18351804
PLoS Comput Biol. 2008 Nov;4(11):e1000216
18989395
Annu Rev Biochem. 2009;78:245-71
19317649
Nature. 1997 Sep 18;389(6648):251-60
9305837
Nature. 2009 Mar 19;458(7236):362-6
19092803
Trends Genet. 2009 Aug;25(8):335-43
19596482
PLoS Biol. 2005 Oct;3(10):e328
16122352
Genome Res. 2010 Jan;20(1):59-67
19858362
Nucleic Acids Res. 2009 Aug;37(14):4707-22
19509309
Cell. 1999 Aug 6;98(3):285-94
10458604
Nat Rev Genet. 2009 Mar;10(3):161-72
19204718
Nucleic Acids Res. 1988 Jul 25;16(14A):6677-90
3399412
Genome Res. 2008 Jul;18(7):1073-83
18550805
Nucleic Acids Res. 1981 Jun 25;9(12):2659-73
6269057
Mol Cell. 2005 Jun 10;18(6):735-48
15949447
Nature. 2006 Aug 17;442(7104):772-8
16862119