Histone H4 lysine 12 acetylation regulates telomeric heterochromatin plasticity in Saccharomyces cerevisiae.
Recent studies have established that the highly condensed and transcriptionally silent heterochromatic domains in budding yeast are virtually dynamic structures. The underlying mechanisms for heterochromatin dynamics, however, remain obscure. In this study, we show that histones are dynamically acetylated on H4K12 at telomeric heterochromatin, and this acetylation regulates several of the dynamic telomere properties. Using a de novo heterochromatin formation assay, we surprisingly found that acetylated H4K12 survived the formation of telomeric heterochromatin. Consistently, the histone acetyltransferase complex NuA4 bound to silenced telomeric regions and acetylated H4K12. H4K12 acetylation prevented the over-accumulation of Sir proteins at telomeric heterochromatin and elimination of this acetylation caused defects in multiple telomere-related processes, including transcription, telomere replication, and recombination. Together, these data shed light on a potential histone acetylation mark within telomeric heterochromatin that contributes to telomere plasticity.
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Bo O
BO
Zhou
Shan-Shan
SS
Wang
Yang
Y
Zhang
Xiao-Hong
XH
Fu
Wei
W
Dang
Brian A
BA
Lenzmeier
Jin-Qiu
JQ
Zhou
D000107:Acetylation; D004261:DNA Replication; D006570:Heterochromatin / Q000235:genetics*; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics*; D014158:Transcription, Genetic
D006570:Heterochromatin; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; C496551:Esa1 protein, S cerevisiae; D051548:Histone Acetyltransferases; D019098:Telomerase; D008239:Lysine
Genes Dev. 1992 Feb;6(2):197-210
1737616
EMBO J. 2009 May 20;28(10):1466-78
19369944
Nucleic Acids Res. 2009 Jun;37(11):3699-713
19372273
Annu Rev Biochem. 2007;76:75-100
17362198
Science. 2001 Jan 26;291(5504):646-50
11158676
Cell. 1993 Nov 5;75(3):543-55
8221893
Nat Genet. 2002 Nov;32(3):370-7
12410229
Genes Dev. 1997 Jan 1;11(1):83-93
9000052
Genes Dev. 2002 Jun 15;16(12):1528-39
12080091
Nature. 2002 Sep 26;419(6905):411-5
12353039
PLoS Genet. 2008 Nov;4(11):e1000247
18989454
Mol Cell Biol. 2005 Jun;25(12):4903-13
15923609
J Biol Chem. 2002 Feb 15;277(7):4778-81
11714726
Mol Biol Cell. 2006 Apr;17(4):1744-57
16436512
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3561-5
9520405
Genes Dev. 2009 Apr 15;23(8):928-38
19390087
Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5501-6
15795371
Genes Dev. 2001 Dec 1;15(23):3169-82
11731480
Mol Cell. 2001 Aug;8(2):473-9
11545749
Nat Cell Biol. 2009 Nov;11(11):1376-82
19783983
Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14503-8
8962081
Proc Natl Acad Sci U S A. 2002 Dec 10;99 Suppl 4:16454-61
12196632
Genes Dev. 2006 Mar 15;20(6):700-10
16543222
Cell. 2005 Jan 14;120(1):37-48
15652480
PLoS One. 2009 Jul 23;4(7):e6363
19626119
Genetics. 2003 Sep;165(1):115-25
14504221
Mol Cell Biol. 2010 May;30(10):2391-400
20308321
Cell. 1990 Nov 16;63(4):751-62
2225075
Anal Biochem. 2003 May 1;316(1):23-33
12694723
J Biol Chem. 1998 Apr 17;273(16):9388-92
9545262
J Biol Chem. 1995 Oct 20;270(42):24674-7
7559580
Nature. 2000 Feb 17;403(6771):795-800
10693811
Science. 2001 Jan 26;291(5504):650-3
11158677
Cell. 2001 May 4;105(3):403-14
11348596
Nat Rev Genet. 2007 Apr;8(4):299-309
17363977
EMBO J. 2005 Jun 15;24(12):2138-49
15920479
Genes Dev. 2000 Feb 15;14(4):452-63
10691737
Nature. 2001 Jan 4;409(6816):109-13
11343124
Mol Cell. 2006 Apr 21;22(2):179-92
16630888
Cell. 1999 Dec 23;99(7):723-33
10619426
J Biol Chem. 1998 May 15;273(20):12599-605
9575221
Cell. 2003 Mar 7;112(5):725-36
12628191
Biochem Biophys Res Commun. 2009 Dec 25;390(4):1355-60
19895790
Cell. 1995 Feb 24;80(4):583-92
7867066
Genes Dev. 2007 Feb 1;21(3):292-302
17289918
Mol Cell. 2000 Dec;6(6):1297-307
11163204
Cell. 1992 Apr 17;69(2):375-84
1568251
Genetics. 2009 Sep;183(1):149-60
19596907
Mol Cell Biol. 2007 Aug;27(16):5639-49
17562861
Nucleic Acids Res. 2007;35(3):822-38
17202155
Mol Cell Biol. 2002 Jun;22(12):4167-80
12024030
Mol Cell Biol. 1996 Aug;16(8):4349-56
8754835
Nucleic Acids Res. 2007;35(9):3109-17
17452364
Mol Cell Biol. 2008 Apr;28(7):2257-70
18212047
J Biol Chem. 2010 May 21;285(21):15966-77
20332092
EMBO J. 2010 Jan 6;29(1):158-70
19875981
Genes Dev. 2003 Jun 1;17(11):1415-28
12782659
Nat Genet. 2002 Nov;32(3):378-83
12379856
Genes Dev. 2010 Apr 1;24(7):647-52
20299449
Curr Opin Genet Dev. 2001 Apr;11(2):199-204
11250144
Annu Rev Biochem. 2003;72:481-516
12676793
Mol Cell Biol. 2000 Nov;20(21):7991-8000
11027269