Home LiteratureArticle Details
PMID: 22012258 Published · epublish English Journal Article Research Support, American Recovery and Reinvestment Act Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans.

Nature ·Vol. 479 ·No. 7373 ·2011-10-19 ·Pages 365-71

Greer EL, Maures TJ, Ucar D, Hauswirth AG, Mancini E, Lim JP, Benayoun BA, Shi Y, Brunet A

Abstract

Chromatin modifiers regulate lifespan in several organisms, raising the question of whether changes in chromatin states in the parental generation could be incompletely reprogrammed in the next generation and thereby affect the lifespan of descendants. The histone H3 lysine 4 trimethylation (H3K4me3) complex, composed of ASH-2, WDR-5 and the histone methyltransferase SET-2, regulates Caenorhabditis elegans lifespan. Here we show that deficiencies in the H3K4me3 chromatin modifiers ASH-2, WDR-5 or SET-2 in the parental generation extend the lifespan of descendants up until the third generation. The transgenerational inheritance of lifespan extension by members of the ASH-2 complex is dependent on the H3K4me3 demethylase RBR-2, and requires the presence of a functioning germline in the descendants. Transgenerational inheritance of lifespan is specific for the H3K4me3 methylation complex and is associated with epigenetic changes in gene expression. Thus, manipulation of specific chromatin modifiers only in parents can induce an epigenetic memory of longevity in descendants.

MeSH Terms
Animals Caenorhabditis elegans/genetics,physiology Caenorhabditis elegans Proteins/genetics,metabolism Chromatin/metabolism Epigenesis, Genetic/genetics Female Gene Expression Regulation Gene Knockdown Techniques Histone Demethylases/genetics,metabolism Histone-Lysine N-Methyltransferase/deficiency,genetics,metabolism Histones Inheritance Patterns Longevity/genetics,physiology Male Methylation Mutation/genetics Nuclear Proteins/genetics,metabolism Pedigree Retinoblastoma-Binding Protein 2/genetics,metabolism
Chemicals
Caenorhabditis elegans Proteins Chromatin Histones Nuclear Proteins SET-2 protein, C elegans wdr-5.1 protein, C elegans Histone Demethylases RBR-2 protein, C elegans Retinoblastoma-Binding Protein 2 ASH-2 protein, C elegans Histone-Lysine N-Methyltransferase
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Greer Eric L
Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.
Maures Travis J
Ucar Duygu
Hauswirth Anna G
Mancini Elena
Lim Jana P
Benayoun Bérénice A
Shi Yang
Brunet Anne
References (53)
53 references, click to expand
  1. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans.
    Nature. 2003 Jul 17;424(6946):277-83 PMID: 12845331
  2. An epigenetic mutation responsible for natural variation in floral symmetry.
    Nature. 1999 Sep 9;401(6749):157-61 PMID: 10490023
  3. Lifespan regulation by evolutionarily conserved genes essential for viability.
    PLoS Genet. 2007 Apr 6;3(4):e56 PMID: 17411345
  4. Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling.
    Cell. 2006 Mar 10;124(5):1055-68 PMID: 16530050
  5. RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse.
    Nature. 2006 May 25;441(7092):469-74 PMID: 16724059
  6. Rapid coevolution of the nematode sex-determining genes fem-3 and tra-2.
    Curr Biol. 2002 Dec 10;12(23):2035-41 PMID: 12477393
  7. Rates of behavior and aging specified by mitochondrial function during development.
    Science. 2002 Dec 20;298(5602):2398-401 PMID: 12471266
  8. Glucose metabolism is altered in the adequately-nourished grand-offspring (F3 generation) of rats malnourished during gestation and perinatal life.
    Diabetologia. 2006 May;49(5):1117-9 PMID: 16557373
  9. Antagonistic functions of SET-2/SET1 and HPL/HP1 proteins in C. elegans development.
    Dev Biol. 2007 Dec 1;312(1):367-83 PMID: 17967446
  10. The Drosophila Fab-7 chromosomal element conveys epigenetic inheritance during mitosis and meiosis.
    Cell. 1998 May 15;93(4):505-18 PMID: 9604927
  11. Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.
    Science. 2010 Dec 24;330(6012):1775-87 PMID: 21177976
  12. A role for Set1/MLL-related components in epigenetic regulation of the Caenorhabditis elegans germ line.
    PLoS Genet. 2011 Mar;7(3):e1001349 PMID: 21455483
  13. Methylation and demethylation activities of a C. elegans MLL-like complex attenuate RAS signalling.
    Dev Biol. 2010 May 1;341(1):142-53 PMID: 20188723
  14. The histone H3K36 methyltransferase MES-4 acts epigenetically to transmit the memory of germline gene expression to progeny.
    PLoS Genet. 2010 Sep 02;6(9):e1001091 PMID: 20824077
  15. ChIPOTle: a user-friendly tool for the analysis of ChIP-chip data.
    Genome Biol. 2005;6(11):R97 PMID: 16277752
  16. An MLL/COMPASS subunit functions in the C. elegans dosage compensation complex to target X chromosomes for transcriptional regulation of gene expression.
    Genes Dev. 2011 Mar 1;25(5):499-515 PMID: 21363964
  17. Caenorhabditis elegans chromatin-associated proteins SET-2 and ASH-2 are differentially required for histone H3 Lys 4 methylation in embryos and adult germ cells.
    Proc Natl Acad Sci U S A. 2011 May 17;108(20):8305-10 PMID: 21527717
  18. Epigenetic inheritance of active chromatin after removal of the main transactivator.
    Science. 1999 Oct 29;286(5441):955-8 PMID: 10542150
  19. An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans.
    Curr Biol. 2007 Oct 9;17(19):1646-56 PMID: 17900900
  20. Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan.
    Aging Cell. 2007 Aug;6(4):489-503 PMID: 17608836
  21. Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans.
    Nature. 2010 Jul 15;466(7304):383-7 PMID: 20555324
  22. A C. elegans LSD1 demethylase contributes to germline immortality by reprogramming epigenetic memory.
    Cell. 2009 Apr 17;137(2):308-20 PMID: 19379696
  23. Regulation of MLL1 H3K4 methyltransferase activity by its core components.
    Nat Struct Mol Biol. 2006 Aug;13(8):713-9 PMID: 16878130
  24. Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring.
    Nature. 2010 Oct 21;467(7318):963-6 PMID: 20962845
  25. A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity.
    Nat Genet. 2003 Jan;33(1):40-8 PMID: 12447374
  26. Broad chromosomal domains of histone modification patterns in C. elegans.
    Genome Res. 2011 Feb;21(2):227-36 PMID: 21177964
  27. PGL-1, a predicted RNA-binding component of germ granules, is essential for fertility in C. elegans.
    Cell. 1998 Sep 4;94(5):635-45 PMID: 9741628
  28. A Genetic Change Associated with the R Locus in Maize Which Is Directed and Potentially Reversible.
    Genetics. 1956 Nov;41(6):872-89 PMID: 17247669
  29. Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes.
    Nat Struct Mol Biol. 2006 Sep;13(9):852-4 PMID: 16892064
  30. A C. elegans mutant that lives twice as long as wild type.
    Nature. 1993 Dec 2;366(6454):461-4 PMID: 8247153
  31. Transgenerational response to nutrition, early life circumstances and longevity.
    Eur J Hum Genet. 2007 Jul;15(7):784-90 PMID: 17457370
  32. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals.
    Cell. 2010 Dec 23;143(7):1084-96 PMID: 21183072
  33. Histone H4 lysine 16 acetylation regulates cellular lifespan.
    Nature. 2009 Jun 11;459(7248):802-7 PMID: 19516333
  34. The conserved NAD(H)-dependent corepressor CTBP-1 regulates Caenorhabditis elegans life span.
    Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1496-501 PMID: 19164523
  35. A systematic RNAi screen for longevity genes in C. elegans.
    Genes Dev. 2005 Jul 1;19(13):1544-55 PMID: 15998808
  36. Methylation of H3K4 Is required for inheritance of active transcriptional states.
    Curr Biol. 2010 Mar 9;20(5):397-406 PMID: 20188556
  37. Trans-generational epigenetic regulation of C. elegans primordial germ cells.
    Epigenetics Chromatin. 2010 Aug 12;3(1):15 PMID: 20704745
  38. Mechanisms of epigenetic inheritance.
    Curr Opin Cell Biol. 2007 Jun;19(3):266-72 PMID: 17466502
  39. Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice.
    PLoS Genet. 2006 Apr;2(4):e49 PMID: 16604157
  40. A spatial and temporal map of C. elegans gene expression.
    Genome Res. 2011 Feb;21(2):325-41 PMID: 21177967
  41. Regulation of life-span by germ-line stem cells in Caenorhabditis elegans.
    Science. 2002 Jan 18;295(5554):502-5 PMID: 11799246
  42. Significance analysis of microarrays applied to the ionizing radiation response.
    Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21 PMID: 11309499
  43. Active DNA demethylation: many roads lead to Rome.
    Nat Rev Mol Cell Biol. 2010 Sep;11(9):607-20 PMID: 20683471
  44. Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway.
    Cell Metab. 2011 Aug 3;14(2):161-72 PMID: 21803287
  45. Inheritance of stress-induced, ATF-2-dependent epigenetic change.
    Cell. 2011 Jun 24;145(7):1049-61 PMID: 21703449
  46. Pvclust: an R package for assessing the uncertainty in hierarchical clustering.
    Bioinformatics. 2006 Jun 15;22(12):1540-2 PMID: 16595560
  47. Polycomb Repressive Complex 2 and Trithorax modulate Drosophila longevity and stress resistance.
    Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):169-74 PMID: 20018689
  48. The H3K27 demethylase UTX-1 regulates C. elegans lifespan in a germline-independent, insulin-dependent manner.
    Aging Cell. 2011 Dec;10(6):980-90 PMID: 21834846
  49. A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span.
    Dev Cell. 2001 Dec;1(6):841-51 PMID: 11740945
  50. Epigenetic inheritance at the agouti locus in the mouse.
    Nat Genet. 1999 Nov;23(3):314-8 PMID: 10545949
  51. Pharmacogenetic analysis of lithium-induced delayed aging in Caenorhabditis elegans.
    J Biol Chem. 2008 Jan 4;283(1):350-357 PMID: 17959600
  52. Initiation, establishment, and maintenance of heritable MuDR transposon silencing in maize are mediated by distinct factors.
    PLoS Biol. 2006 Oct;4(10):e339 PMID: 16968137
  53. Asymmetric arginine dimethylation determines life span in C. elegans by regulating forkhead transcription factor DAF-16.
    Cell Metab. 2011 May 4;13(5):505-16 PMID: 21531333
Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature10572
Published
2011-10-19
Epub
2011-00-19
Pages
365-71
Language
English
Region
England
NLM ID
0410462
PMCID
PMC3368121
Subset
IM
Grants
NIGMS NIH HHS · R01-GM058012 · United States
NCI NIH HHS · T32 CA009302 · United States
NIA NIH HHS · F32-AG037254 · United States
NIA NIH HHS · F32 AG037254 · United States
NIA NIH HHS · R01 AG031198 · United States
NIA NIH HHS · R01-AG31198 · United States
NCI NIH HHS · T32 CA009361 · United States
NIMH NIH HHS · T32 MH020016 · United States
NCI NIH HHS · T32-CA009361 · United States
NIMH NIH HHS · T32-MH020016 · United States
NIA NIH HHS · ARRA-AG31198 · United States
NIGMS NIH HHS · R01 GM058012 · United States
NIA NIH HHS · R56 AG031198 · United States
Databases
GEO
GSE30789, GSE31043
Corrections
CommentIn
PMID: 22048661
CommentIn
PMID: 22094684
CommentIn
PMID: 22225870
External Links
PubMed source DOI: 10.1038/nature10572 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2