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Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans

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  • Eric L. Greer

    (Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA
    Cancer Biology Graduate Program, Stanford University, Stanford, California 94305, USA)

  • Travis J. Maures

    (Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA)

  • Anna G. Hauswirth

    (Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA)

  • Erin M. Green

    (Stanford University, Stanford, California 94305, USA)

  • Dena S. Leeman

    (Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA
    Cancer Biology Graduate Program, Stanford University, Stanford, California 94305, USA)

  • Géraldine S. Maro

    (Stanford University, Stanford, California 94305, USA)

  • Shuo Han

    (Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA)

  • Max R. Banko

    (Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA)

  • Or Gozani

    (Cancer Biology Graduate Program, Stanford University, Stanford, California 94305, USA
    Stanford University, Stanford, California 94305, USA)

  • Anne Brunet

    (Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA
    Cancer Biology Graduate Program, Stanford University, Stanford, California 94305, USA)

Abstract

Methylation adds to lifespan Genes of the Sir2 family are known to influence longevity in yeast, in the worm Caenorhabditis elegans and in other organisms through an effect on histone deacetylation. This raises the question of whether other histone modifications also influence longevity. Greer et al. show that histone methylation regulates lifespan determination in C. elegans. Deficiencies in components of a conserved chromatin protein complex known as the ASH-2 complex, which trimethylates histone H3 at lysine 4 (H3K4), all extend worm lifespan. Conversely, the H3K4 demethylase RBR-2 is required for normal lifespan, consistent with the idea that an excess of H3K4 trimethylation shortens lifespan. This increase in longevity requires the presence of an intact adult germline and the continuous production of mature eggs, which suggests that the lifespan of the soma is regulated by an H3K4 methyltransferase/demethylase complex in the germline.

Suggested Citation

  • Eric L. Greer & Travis J. Maures & Anna G. Hauswirth & Erin M. Green & Dena S. Leeman & Géraldine S. Maro & Shuo Han & Max R. Banko & Or Gozani & Anne Brunet, 2010. "Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans," Nature, Nature, vol. 466(7304), pages 383-387, July.
    • Handle: RePEc:nat:nature:v:466:y:2010:i:7304:d:10.1038_nature09195
    DOI: 10.1038/nature09195
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    Cited by:

    1. Xinhao Hou & Mingjing Xu & Chengming Zhu & Jianing Gao & Meili Li & Xiangyang Chen & Cheng Sun & Björn Nashan & Jianye Zang & Ying Zhou & Shouhong Guang & Xuezhu Feng, 2023. "Systematic characterization of chromodomain proteins reveals an H3K9me1/2 reader regulating aging in C. elegans," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Shengjie Fan & Yingxuan Yan & Ying Xia & Zhenyu Zhou & Lingling Luo & Mengnan Zhu & Yongli Han & Deqiang Yao & Lijun Zhang & Minglv Fang & Lina Peng & Jing Yu & Ying Liu & Xiaoyan Gao & Huida Guan & H, 2023. "Pregnane X receptor agonist nomilin extends lifespan and healthspan in preclinical models through detoxification functions," Nature Communications, Nature, vol. 14(1), pages 1-23, December.

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