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Author Notes:

Correspondence: William G. Kelly; Telephone: (404) 727-6461; Fax: (404) 727-2880; E-mail: bkelly@biology.emory.edu

Acknowledgments: We thank R. Baumeister for providing strains; A. Printz for help with data presentation; C. Bean, B. Lakowski, G. Reuter, T. Schedl, Y. Shi and J. Waddle for helpful discussions on the work; T. Caspary, J. Lucchesi and S. Tilghman for critical comments on the manuscript; and all of our laboratory members for assistance throughout.

Subject:

Research Funding:

This work was supported by grants from the NIH to DJK and WGK.

Keywords:

  • epigenetics
  • reprogramming
  • chromatin
  • germline
  • germ cells
  • C. elegans
  • histone demethylase
  • LSD1
  • SPR-5
  • KDM1

A C. elegans LSD1 Demethylase Contributes to Germline Immortality by Reprogramming Epigenetic Memory

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Journal Title:

Cell

Volume:

Volume 137, Number 2

Publisher:

, Pages 308-320

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Recently it has been proposed that di-methylation of histone H3 on lysine 4 (H3K4me2) acts as an epigenetic memory to maintain transcriptional patterns in developing tissues. This model suggests that there may be a requirement to reprogram this modification in the germline to prevent transcriptional memory from being inappropriately transmitted to the next generation. We asked if SPR-5, the C. elegans ortholog of the H3K4me2 demethylase LSD1/KDM1, plays a role in epigenetically reprogramming H3K4me2. We show that spr-5 mutants exhibit progressive sterility over many generations due to defects in oogenesis and spermatogenesis. These defects correlate with a progressive failure to erase H3K4me2 in the primordial germ cells, resulting in the misregulation of spermatogenesis-expressed genes due to the transgenerational accumulation of H3K4me2 at these loci. These results suggest that H3K4me2 can serve as an epigenetic memory and that LSD1/KDM1 demethylases play a critical role in the reprogramming of this memory in the germline, preventing inappropriate epigenetic information from being propagated from one generation to the next.

Copyright information:

© 2009, Elsevier

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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