1. Cell Biology
  2. Developmental Biology and Stem Cells
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Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

  1. Chih-Yung Sean Lee
  2. Tu Lu
  3. Geraldine Seydoux Is a corresponding author
  1. Johns Hopkins University, United States
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Cite as: eLife 2017;6:e30201 doi: 10.7554/eLife.30201

Abstract

Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNA and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.

Article and author information

Author details

  1. Chih-Yung Sean Lee

    Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-0982-2150
  2. Tu Lu

    Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Geraldine Seydoux

    Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, United States
    For correspondence
    gseydoux@jhmi.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0001-8257-0493

Funding

National Institutes of Health (R01HD37047)

  • Geraldine Seydoux

Howard Hughes Medical Institute

  • Geraldine Seydoux

Damon Runyon Cancer Research Foundation (DRG-2417‐13)

  • Chih-Yung Sean Lee

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Julie Ahringer, Reviewing Editor, University of Cambridge, United Kingdom

Publication history

  1. Received: July 6, 2017
  2. Accepted: November 6, 2017
  3. Accepted Manuscript published: November 7, 2017 (version 1)

Copyright

© 2017, Lee et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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