Global regulation of H2A.Z localization by the INO80 chromatin-remodeling enzyme is essential for genome integrity.
INO80 is an evolutionarily conserved, ATP-dependent chromatin-remodeling enzyme that plays roles in transcription, DNA repair, and replication. Here, we show that yeast INO80 facilitates these diverse processes at least in part by controlling genome-wide distribution of the histone variant H2A.Z. In the absence of INO80, H2A.Z nucleosomes are mislocalized, and H2A.Z levels at promoters show reduced responsiveness to transcriptional changes, suggesting that INO80 controls H2A.Z dynamics. Additionally, we demonstrate that INO80 has a histone-exchange activity in which the enzyme can replace nucleosomal H2A.Z/H2B with free H2A/H2B dimers. Genetic interactions between ino80 and htz1 support a model in which INO80 catalyzes the removal of unacetylated H2A.Z from chromatin as a mechanism to promote genome stability.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Manolis
M
Papamichos-Chronakis
Shinya
S
Watanabe
Oliver J
OJ
Rando
Craig L
CL
Peterson
D042002:Chromatin Assembly and Disassembly; D016681:Genome, Fungal; D042822:Genomic Instability; D006657:Histones / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
D006657:Histones; C483404:INO80 complex, S cerevisiae; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins
Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18147-52
15608061
Mol Cell. 2004 Nov 19;16(4):655-61
15546624
Genes Dev. 2006 Mar 15;20(6):711-22
16543223
Nat Struct Mol Biol. 2009 Dec;16(12):1286-93
19915592
Science. 2005 Jul 22;309(5734):626-30
15961632
Science. 2008 Mar 7;319(5868):1352-5
18323444
Methods Enzymol. 1999;304:3-19
10372352
Genes Dev. 2006 Sep 1;20(17):2437-49
16951256
Cell. 2007 Aug 10;130(3):499-511
17693258
Genes Dev. 2004 Mar 15;18(6):602-16
15075289
Genes Dev. 2006 Mar 15;20(6):660-5
16543219
Trends Biochem Sci. 2009 Feb;34(2):71-7
19062292
Mol Cell Biol. 1996 Aug;16(8):3990-4002
8754797
PLoS Biol. 2004 May;2(5):E131
15045029
Cell. 2009 Sep 18;138(6):1109-21
19766565
Nat Struct Mol Biol. 2007 Dec;14(12):1165-72
18026119
Nat Struct Mol Biol. 2008 May;15(5):477-84
18408730
Genes Dev. 2006 Mar 15;20(6):700-10
16543222
Nature. 2007 Mar 29;446(7135):572-6
17392789
Oncogene. 2002 May 9;21(20):3253-7
12082642
Science. 2004 Jan 16;303(5656):343-8
14645854
Mol Cancer Res. 2002 Dec;1(2):103-12
12496357
Nat Struct Biol. 2002 Mar;9(3):172-6
11850638
Annu Rev Biochem. 2009;78:273-304
19355820
Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21573-8
19966225
Cell. 2005 Oct 21;123(2):219-31
16239141
Curr Biol. 2008 Apr 22;18(8):566-75
18406137
Mol Cell. 2001 Jun;7(6):1329-35
11430834
Methods Mol Biol. 1999;119:1-16
10804500
Cell Cycle. 2010 Jan 15;9(2):364-70
20023423
Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9309-14
15184677
Nat Rev Mol Cell Biol. 2010 Apr;11(4):264-75
20197778
Mol Cell. 2003 Dec;12(6):1565-76
14690608
Genome Res. 2009 Mar;19(3):360-71
19124666
Nat Struct Mol Biol. 2008 Apr;15(4):338-45
18376411
Nat Struct Mol Biol. 2005 Dec;12(12):1064-71
16299513
Cell. 2003 Mar 7;112(5):725-36
12628191
Biochemistry. 2006 May 2;45(17):5671-7
16634648
Mol Cell. 2003 Jul;12(1):147-55
12887900
PLoS Genet. 2009 Oct;5(10):e1000687
19834540
Methods Enzymol. 1999;304:726-41
10372393
Nature. 2000 Aug 3;406(6795):541-4
10952318
Genes Dev. 2008 Aug 1;22(15):2062-74
18676811
Cell. 2007 Feb 23;128(4):721-33
17320509
Nat Rev Mol Cell Biol. 2009 Jun;10(6):373-84
19424290
Genes Dev. 1997 Dec 15;11(24):3375-86
9407030
Cell Mol Life Sci. 2010 Jul;67(13):2283-96
20237820
Mol Cell Biol. 2009 Sep;29(18):4994-5007
19620280
PLoS Biol. 2005 Oct;3(10):e328
16122352
Nature. 2008 May 15;453(7193):358-62
18408708
Cell. 2005 Oct 21;123(2):233-48
16239142