HST3/HST4-dependent deacetylation of lysine 56 of histone H3 in silent chromatin.
The composition of posttranslational modifications on newly synthesized histones must be altered upon their incorporation into chromatin. These changes are necessary to maintain the same gene expression state at individual chromosomal loci before and after DNA replication. We have examined how one modification that occurs on newly synthesized histone H3, acetylation of K56, influences gene expression at epigenetically regulated loci in Saccharomyces cerevisiae. H3 K56 is acetylated by Rtt109p before its incorporation into chromatin during S phase, and this modification is then removed by the NAD(+)-dependent deacetylases Hst3p and Hst4p during G2/M phase. We found silenced loci maintain H3 K56 in a hypoacetylated state, and the absence of this modification in rtt109 mutants was compatible with HM and telomeric silencing. In contrast, loss of HST3 and HST4 resulted in hyperacetylation of H3 K56 within silent loci and telomeric silencing defects, despite the continued presence of Sir2p throughout these loci. These silencing defects in hst3Delta hst4Delta mutants could be suppressed by deletion of RTT109. In contrast, overexpression of Sir2p could not restore silencing in hst3Delta hst4Delta mutants. Together, our findings argue that HST3 HST4 play critical roles in maintaining the hypoacetylated state of K56 on histone H3 within silent chromatin.
Yang
Bo
B
Department of Biochemistry and Purdue Cancer Center, Purdue University, West Lafayette, IN 47907, USA.
Miller
Andrew
A
Kirchmaier
Ann L
AL
D000107:Acetylation; D002843:Chromatin / Q000378:metabolism*; D049770:Genes, Mating Type, Fungal; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism; D056565:Sirtuin 2; D037761:Sirtuins / Q000378:metabolism; D016615:Telomere / Q000201:enzymology
D002843:Chromatin; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C512517:Hst3 protein, S cerevisiae; C512518:Hst4 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; D008239:Lysine
Nature. 2005 Jul 14;436(7048):294-8
16015338
Cell. 2005 May 6;121(3):375-85
15882620
Yeast. 1994 Dec;10(13):1793-808
7747518
J Biol Chem. 2007 May 18;282(20):15040-7
17369611
Methods Enzymol. 2002;350:165-86
12073311
EMBO J. 2005 Jun 15;24(12):2138-49
15920479
Genes Dev. 2002 Nov 15;16(22):2935-45
12435634
Mol Cell Biol. 2006 Feb;26(3):852-62
16428441
Genetics. 2006 Aug;173(4):1939-50
16783021
Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13004-9
16916930
Nat Genet. 2001 Aug;28(4):327-34
11455386
Mol Cell Biol. 2005 Nov;25(22):10060-70
16260619
J Biol Chem. 2007 Dec 28;282(52):37805-14
17977840
Mol Cell Biol. 2000 Oct;20(19):7051-8
10982821
EMBO J. 2007 May 16;26(10):2477-88
17446861
Genetics. 2004 Sep;168(1):65-75
15454527
Mol Biol Cell. 2002 Jul;13(7):2207-22
12134062
Biochemistry. 2006 Mar 7;45(9):2852-61
16503640
J Biol Chem. 2007 May 11;282(19):14158-64
17369253
Cell. 1990 Nov 16;63(4):751-62
2225075
Science. 2007 Feb 2;315(5812):653-5
17272723
Yeast. 1986 Sep;2(3):163-7
3333305
Mol Biol Cell. 2006 Dec;17(12):5287-97
17035629
Mol Cell. 2007 Aug 3;27(3):393-405
17679090
Science. 2001 Oct 5;294(5540):115-21
11588253
Science. 2001 Jan 26;291(5504):646-50
11158676
Mol Cell Biol. 1997 Nov;17(11):6693-9
9343433
Nature. 2000 Feb 17;403(6771):795-800
10693811
Science. 2001 Jan 26;291(5504):650-3
11158677
Mol Cell. 2006 Jul 7;23(1):109-19
16818235
Mol Cell. 2007 Dec 28;28(6):1015-28
18158899
Eukaryot Cell. 2008 May;7(5):800-13
18344406
Gene. 1992 Jan 2;110(1):119-22
1544568
Genetics. 2008 Jun;179(2):793-809
18558650
Nucleic Acids Res. 1990 May 25;18(10):3091-2
2190191
Nat Genet. 2002 Nov;32(3):370-7
12410229
Genetics. 1999 Sep;153(1):25-33
10471697
J Struct Biol. 2000 Apr;129(2-3):159-74
10806066
J Biol Chem. 2007 Sep 28;282(39):28587-28596
17690098
Cell. 2005 May 20;121(4):515-527
15907466
Genes Dev. 1997 Jan 1;11(1):83-93
9000052
Cell. 1991 Sep 20;66(6):1279-87
1913809
Nature. 1984 Nov 15-21;312(5991):247-51
6390211
Genetics. 1997 Apr;145(4):923-34
9093847
Mol Cell. 2007 Sep 21;27(6):890-900
17889663
Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):415-20
11134535
Genes Dev. 2002 Jun 15;16(12):1528-39
12080091
J Mol Biol. 2008 Sep 12;381(4):826-44
18619469
Science. 2007 Feb 2;315(5812):649-52
17272722
Mol Biol Cell. 1999 Oct;10(10):3171-86
10512858
Curr Biol. 2006 Jul 11;16(13):1280-9
16815704
Genetics. 1997 Mar;145(3):605-14
9055071
Mol Cell Biol. 2008 Jul;28(13):4342-53
18458063
Mol Biol Cell. 1999 Sep;10(9):3045-59
10473645
Arch Biochem Biophys. 2008 Jan 15;469(2):157-64
18036332
Yeast. 1999 Oct;15(14):1541-53
10514571
Mol Cell Biol. 2002 Jun;22(12):4167-80
12024030
Science. 1997 Jun 6;276(5318):1547-51
9171055
Nature. 1997 Sep 18;389(6648):251-60
9305837
J Biol Chem. 2006 Dec 8;281(49):37270-4
17046836
Genetics. 2002 Sep;162(1):59-71
12242223
Mol Cell. 2007 Mar 9;25(5):703-12
17320445
Proc Natl Acad Sci U S A. 2006 May 2;103(18):6988-93
16627621
Nat Genet. 2002 Nov;32(3):378-83
12379856
J Biol Chem. 2005 Jul 15;280(28):25949-52
15888442
Genes Dev. 1995 Dec 1;9(23):2888-902
7498786
Cell Cycle. 2006 Nov;5(22):2602-8
17172838
Nature. 2007 Apr 12;446(7137):806-10
17314980
Annu Rev Biochem. 2003;72:481-516
12676793
Genes Dev. 1994 May 15;8(10):1133-46
7926719
J Biol Chem. 2004 Jun 25;279(26):26830-8
15078868
J Biol Chem. 2007 Mar 9;282(10):7641-55
17194708