Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B
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.
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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
- Julie Ahringer, University of Cambridge, United Kingdom
Version history
- Received: July 6, 2017
- Accepted: November 6, 2017
- Accepted Manuscript published: November 7, 2017 (version 1)
- Version of Record published: December 18, 2017 (version 2)
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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