title: Trimethylation of Lys36 on H3 restricts gene expression change during aging and impacts life span.
abstract: Functional data indicate that specific histone modification enzymes can be key to longevity in Caenorhabditis elegans, but the molecular basis of how chromatin structure modulates longevity is not well understood. In this study, we profiled the genome-wide pattern of trimethylation of Lys36 on histone 3 (H3K36me3) in the somatic cells of young and old Caenorhabditis elegans. We revealed a new role of H3K36me3 in maintaining gene expression stability through aging with important consequences on longevity. We found that genes with dramatic expression change during aging are marked with low or even undetectable levels of H3K36me3 in their gene bodies irrespective of their corresponding mRNA abundance. Interestingly, 3' untranslated region (UTR) length strongly correlates with H3K36me3 levels and age-dependent mRNA expression stability. A similar negative correlation between H3K36me3 marking and mRNA expression change during aging was also observed in Drosophila melanogaster, suggesting a conserved mechanism for H3K36me3 in suppressing age-dependent mRNA expression change. Importantly, inactivation of the methyltransferase met-1 resulted in a decrease in global H3K36me3 marks, an increase in mRNA expression change with age, and a shortened life span, suggesting a causative role of the H3K36me3 marking in modulating age-dependent gene expression stability and longevity.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA;
authors.forename: Mintie
authors.initials: M
authors.lastname: Pu
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA;
authors.forename: Zhuoyu
authors.initials: Z
authors.lastname: Ni
authors.affiliation: Computational Biology Service Unit, Cornell University, Ithaca, New York 14850, USA;
authors.forename: Minghui
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA; Department of Biostatistics and Computational Biology, Weill Institute, Cornell University, Ithaca, New York 14850, USA;
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Wood
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Helfand
authors.affiliation: Department of Biostatistics and Computational Biology, Weill Institute, Cornell University, Ithaca, New York 14850, USA;
authors.forename: Haiyuan
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA; sylvia.lee@cornell.edu.
authors.forename: Siu Sylvia
authors.initials: SS
authors.lastname: Lee
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008136:Longevity / Q000235:genetics*; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D008745:Methylation
chemical_list: D006657:Histones; D008239:Lysine
keywords: H3K36me3; aging; epigenetics; gene expression; met-1
references.citation: Nat Biotechnol. 2008 Dec;26(12):1351-9
references.pmid: 19029915
references.citation: Mol Biol Cell. 1999 Oct;10(10):3125-36
references.pmid: 10512855
references.citation: Nature. 2011 Nov 17;479(7373):365-71
references.pmid: 22012258
references.citation: Aging Cell. 2010 Dec;9(6):971-8
references.pmid: 20961390
references.citation: PLoS Genet. 2012;8(5):e1002717
references.pmid: 22615581
references.citation: Cell Metab. 2011 Aug 3;14(2):161-72
references.pmid: 21803287
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):169-74
references.pmid: 20018689
references.citation: J Cell Sci. 2012 Jan 1;125(Pt 1):7-17
references.pmid: 22294612
references.citation: Nat Genet. 2004 Feb;36(2):197-204
references.pmid: 14730301
references.citation: Cell. 2005 Nov 18;123(4):581-92
references.pmid: 16286007
references.citation: PLoS Genet. 2006 Jul;2(7):e115
references.pmid: 16789832
references.citation: Cell. 2005 Aug 26;122(4):517-27
references.pmid: 16122420
references.citation: Genes Dev. 2007 Jun 1;21(11):1422-30
references.pmid: 17545470
references.citation: PLoS Genet. 2007 Apr 6;3(4):e56
references.pmid: 17411345
references.citation: Nature. 2012 Sep 20;489(7416):452-5
references.pmid: 22914091
references.citation: PLoS Genet. 2011 May;7(5):e1002082
references.pmid: 21625567
references.citation: Genome Biol. 2013;14(10):R115
references.pmid: 24138928
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13564-9
references.pmid: 21807997
references.citation: Curr Genomics. 2012 Nov;13(7):548-57
references.pmid: 23633914
references.citation: Genetics. 1974 May;77(1):71-94
references.pmid: 4366476
references.citation: Elife. 2013;2:e00808
references.pmid: 23795297
references.citation: Development. 2007 Aug;134(16):2991-9
references.pmid: 17634190
references.citation: Bioinformatics. 2009 May 1;25(9):1105-11
references.pmid: 19289445
references.citation: Cell. 2003 May 16;113(4):429-32
references.pmid: 12757703
references.citation: Acta Neuropathol. 2013 May;125(5):659-69
references.pmid: 23417712
references.citation: Genome Biol. 2012;13(7):165
references.pmid: 22839706
references.citation: Nat Genet. 2000 Jul;25(3):294-7
references.pmid: 10888876
references.citation: Cell. 2007 May 18;129(4):823-37
references.pmid: 17512414
references.citation: Nat Biotechnol. 2010 May;28(5):511-5
references.pmid: 20436464
references.citation: Nature. 2014 Apr 10;508(7495):263-8
references.pmid: 24590075
references.citation: Bioinformatics. 2009 Aug 15;25(16):2078-9
references.pmid: 19505943
references.citation: Genome Res. 2012 Sep;22(9):1813-31
references.pmid: 22955991
references.citation: Mol Cell. 2010 May 28;38(4):576-89
references.pmid: 20513432
references.citation: Genome Res. 2011 Feb;21(2):325-41
references.pmid: 21177967
references.citation: Front Genet. 2013 Dec 04;4:274
references.pmid: 24363663
references.citation: Genome Res. 2014 Feb;24(2):241-50
references.pmid: 24158655
references.citation: Nat Rev Mol Cell Biol. 2012 Feb;13(2):115-26
references.pmid: 22266761
references.citation: Cell. 2010 Oct 15;143(2):212-24
references.pmid: 20888037
references.citation: Cell. 2007 Feb 23;128(4):693-705
references.pmid: 17320507
references.citation: Nature. 2007 Aug 2;448(7153):553-60
references.pmid: 17603471
references.citation: Science. 1999 Aug 27;285(5432):1390-3
references.pmid: 10464095
references.citation: Genes Dev. 2005 Jul 1;19(13):1544-55
references.pmid: 15998808
references.citation: J Biol Chem. 2008 Jan 4;283(1):350-7
references.pmid: 17959600
references.citation: Aging Cell. 2011 Dec;10(6):980-90
references.pmid: 21834846
references.citation: PLoS One. 2008;3(8):e3024
references.pmid: 18714388
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5093-8
references.pmid: 11309484
references.citation: Nat Genet. 2007 Mar;39(3):403-8
references.pmid: 17293863
references.citation: BMC Genomics. 2012;13 Suppl 7:S14
references.pmid: 23281599
references.citation: Cell. 1987 Nov 20;51(4):601-11
references.pmid: 3677169
references.citation: Genome Biol. 2009;10(3):R25
references.pmid: 19261174
references.citation: Bioinformatics. 2009 Apr 1;25(7):875-81
references.pmid: 19189975
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13726-31
references.pmid: 11095759
references.citation: Nat Struct Mol Biol. 2011 Sep;18(9):977-83
references.pmid: 21792193
references.citation: EMBO J. 2008 Jan 23;27(2):406-20
references.pmid: 18157086
references.citation: Genome Biol. 2013;14(7):R75
references.pmid: 23889843
references.citation: Genome Biol. 2011;12(8):R83
references.pmid: 21859476
references.citation: Cell. 2008 Jul 25;134(2):291-303
references.pmid: 18662544
references.citation: Nature. 2009 Jun 11;459(7248):802-7
references.pmid: 19516333
references.citation: Mol Cell. 2013 Jan 24;49(2):359-67
references.pmid: 23177740
references.citation: Nat Protoc. 2012 Mar;7(3):562-78
references.pmid: 22383036
references.citation: Cell. 2013 Apr 25;153(3):590-600
references.pmid: 23622243
references.citation: Genome Res. 2013 Aug;23(8):1339-47
references.pmid: 23550086
references.citation: Methods. 2003 Aug;30(4):313-21
references.pmid: 12828945
references.citation: Nature. 2010 Jul 15;466(7304):383-7
references.pmid: 20555324
references.citation: F1000Prime Rep. 2014 Feb 03;6:7
references.pmid: 24592319
references.citation: FEBS Lett. 2011 Jul 7;585(13):2041-8
references.pmid: 21081125
references.citation: Bioinformatics. 2009 Jul 15;25(14):1754-60
references.pmid: 19451168
references.citation: Nat Protoc. 2009;4(1):44-57
references.pmid: 19131956
references.citation: BMC Genomics. 2014;15:284
references.pmid: 24735413
references.citation: Science. 2010 Jul 23;329(5990):432-5
references.pmid: 20522740
references.citation: Nat Struct Mol Biol. 2012 Sep;19(9):884-92
references.pmid: 22922743
references.citation: WormBook. 2007;:1-12
references.pmid: 18050504
references.citation: Curr Biol. 2002 Apr 30;12(9):712-23
references.pmid: 12007414
references.citation: Nat Genet. 2009 Mar;41(3):376-81
references.pmid: 19182803
references.citation: Annu Rev Biochem. 2006;75:243-69
references.pmid: 16756492