Widespread remodeling of mid-coding sequence nucleosomes by Isw1.
BACKGROUND
The positions of nucleosomes along eukaryotic DNA are defined by the local DNA sequence and are further tuned by the activity of chromatin remodelers. While the genome-wide effect of most remodelers has not been described, recent studies in Saccharomyces cerevisiae have shown that Isw2 prevents ectopic expression of anti-sense and suppressed transcripts at gene ends.


RESULTS
We examined the genome-wide function of the Isw2 homologue, Isw1, by mapping nucleosome positioning in S. cerevisiae and Saccharomyces paradoxus strains deleted of ISW1. We found that Isw1 functions primarily within coding regions of genes, consistent with its putative role in transcription elongation. Upon deletion of ISW1, mid-coding nucleosomes were shifted upstream (towards the 5' ends) in about half of the genes. Isw1-dependent shifts were correlated with trimethylation of H3K79 and were enriched at genes with internal cryptic initiation sites.


CONCLUSIONS
Our results suggest a division of labor between Isw1 and Isw2, whereby Isw2 maintains repressive chromatin structure at gene ends while Isw1 has a similar function at mid-coding regions. The differential specificity of the two remodelers may be specified through interactions with particular histone marks.
Tirosh
Itay
I
Department of Molecular genetics, Weizmann Institute of Science, Herzl street, Rehovot 76100, Israel. itay.tirosh@weizmann.ac.il
Sigal
Nadejda
N
Barkai
Naama
N
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D045584:Chromosome Positioning / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008957:Models, Genetic; D009707:Nucleosomes / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics*; D012319:RNA Polymerase II / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D024363:Transcription Initiation Site
D004268:DNA-Binding Proteins; D006657:Histones; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D012319:RNA Polymerase II; D000251:Adenosine Triphosphatases; C470546:ISW1 protein, S cerevisiae; D008239:Lysine
Cell. 2007 Feb 23;128(4):707-19
17320508
Cell. 2003 Nov 14;115(4):425-35
14622597
Mol Cell Biol. 2005 Nov;25(21):9165-74
16227570
Genes Dev. 1999 Mar 15;13(6):686-97
10090725
Mol Cell Biol. 2003 Jan;23(1):80-91
12482963
PLoS Biol. 2008 Nov 11;6(11):e277
18998772
Nature. 1997 Sep 18;389(6648):251-60
9305837
Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17846-51
17101987
BMC Bioinformatics. 2006 Mar 07;7:113
16522208
EMBO J. 2000 Nov 15;19(22):6141-9
11080160
Trends Biochem Sci. 1997 Mar;22(3):93-7
9066259
Mol Cell. 2006 May 5;22(3):415-22
16678113
Genome Res. 2006 Dec;16(12):1517-28
17053089
Genome Biol. 2009;10(10):R109
19814794
Nature. 2007 Mar 29;446(7135):572-6
17392789
Nature. 2003 May 15;423(6937):241-54
12748633
Annu Rev Biochem. 2009;78:273-304
19355820
Nat Genet. 2007 Oct;39(10):1235-44
17873876
Mol Cell Biol. 2009 May;29(9):2419-30
19273607
Genetics. 2010 Feb;184(2):321-34
19948887
Cell. 2005 Oct 21;123(2):219-31
16239141
Mol Cell. 2009 Sep 11;35(5):626-41
19682934
Mol Cell Biol. 2003 Nov;23(22):8323-33
14585989
EMBO J. 1986 Oct;5(10):2689-96
3536481
Science. 2005 Jul 22;309(5734):626-30
15961632
PLoS One. 2009;4(3):e4886
19295910
Nat Struct Mol Biol. 2009 Feb;16(2):151-8
19182801
Mol Cell. 2004 Oct 22;16(2):199-209
15494307
Genome Res. 2010 Jan;20(1):90-100
19846608
Genes Dev. 2005 Apr 15;19(8):942-54
15833917
Biochim Biophys Acta. 2004 Mar 15;1677(1-3):100-12
15020051
Mol Cell. 2003 Nov;12(5):1325-32
14636589
Genome Res. 2009 Mar;19(3):360-71
19124666
Cell. 1998 Nov 25;95(5):717-28
9845373
EMBO J. 2007 Nov 14;26(22):4646-56
17948059
Mol Cell Biol. 2005 Dec;25(24):11156-70
16314535
Science. 2003 Aug 22;301(5636):1096-9
12934008
Nature. 2007 Dec 13;450(7172):1031-5
18075583
Mol Cell. 2002 Mar;9(3):541-52
11931762
PLoS Genet. 2006 Sep 22;2(9):e158
17002501
Nat Struct Mol Biol. 2004 Aug;11(8):763-9
15258568
Science. 2009 May 1;324(5927):659-62
19407207
Mol Cell. 2007 Jan 12;25(1):31-42
17218269
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
Mol Cell Biol. 2006 Feb;26(4):1496-509
16449659
Nature. 2009 Mar 19;458(7236):362-6
19092803
Genes Dev. 2001 Mar 1;15(5):619-26
11238381
Genome Res. 2010 Jan;20(1):59-67
19858362
Cell. 2005 Aug 26;122(4):517-27
16122420
Cell. 2005 Oct 21;123(2):233-48
16239142
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
Nature. 2006 Aug 17;442(7104):772-8
16862119
J Mol Biol. 2007 Aug 3;371(1):1-10
17561109