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The H3K27 demethylase UTX-1 regulates C. elegans lifespan in a germline-independent, insulin-dependent manner.

Aging is accompanied by alterations in epigenetic marks that control chromatin states, including histone acetylation and methylation. Enzymes that reversibly affect histone marks associated with active chromatin have recently been found to regulate aging in Caenorhabditis elegans. However, relatively little is known about the importance for aging of histone marks associated with repressed chromatin. Here, we use a targeted RNAi screen in C. elegans to identify four histone demethylases that significantly regulate worm lifespan, UTX-1, RBR-2, LSD-1, and T26A5.5. Interestingly, UTX-1 belongs to a conserved family of histone demethylases specific for lysine 27 of histone H3 (H3K27me3), a mark associated with repressed chromatin. Both utx-1 knockdown and heterozygous mutation of utx-1 extend lifespan and increase the global levels of the H3K27me3 mark in worms. The H3K27me3 mark significantly drops in somatic cells during the normal aging process. UTX-1 regulates lifespan independently of the presence of the germline, but in a manner that depends on the insulin-FoxO signaling pathway. These findings identify the H3K27me3 histone demethylase UTX-1 as a novel regulator of worm lifespan in somatic cells.

Pubmed ID: 21834846

Authors

  • Maures TJ
  • Greer EL
  • Hauswirth AG
  • Brunet A

Journal

Aging cell

Publication Data

December 14, 2011

Associated Grants

  • Agency: NIA NIH HHS, Id: AG31198
  • Agency: NIA NIH HHS, Id: F32-AG037254
  • Agency: NIA NIH HHS, Id: R01 AG031198
  • Agency: NIA NIH HHS, Id: R01 AG031198-01A1
  • Agency: NIA NIH HHS, Id: R01 AG031198-01A1S1
  • Agency: NIA NIH HHS, Id: R01 AG031198-02
  • Agency: NIA NIH HHS, Id: R01 AG031198-03
  • Agency: NIA NIH HHS, Id: R01 AG031198-04
  • Agency: NIA NIH HHS, Id: R01-AG31198
  • Agency: NCI NIH HHS, Id: T32-CA009302
  • Agency: NHGRI NIH HHS, Id: T32-HG000044

Mesh Terms

  • Animals
  • Biological Markers
  • Blotting, Western
  • Caenorhabditis elegans
  • Chromatin
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Germ Cells
  • High-Throughput Screening Assays
  • Histone Demethylases
  • Histones
  • Insulin
  • Longevity
  • Methylation
  • Polymerase Chain Reaction
  • RNA Interference
  • Signal Transduction
  • Transcription Factors