Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

Abstract
Data availability
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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.

Data availability

The following data sets were generated

1. Lee CY
2. Lu T
3. Seydoux G
(2017) Genome-wide maps of chromatin structure in wild-type and nanos mutant primordial germ cells in C.elegans.
reviewer token: ozybkiqidzihjqv.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100651
1. Lee CY
2. Lu T
3. Seydoux G
(2017) Chromatin reprogramming in primordial germ cells requires Nanos-dependent down-regulation of the synMuvB transcription factor LIN-15B
reviewer token: idajemoixjetzmb.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100652

The following previously published data sets were used

1. Ortiz MA
2. Noble D
3. Sorokin EP
4. Kimble J
(2014) A New Dataset of Spermatogenic vs. Oogenic Transcriptomes in the Nematode Caenorhabditis elegans
Supplemental Table S1.

http://www.g3journal.org/highwire/filestream/472440/field_highwire_adjunct_files/0/TableS1.xlsx

Article and author information

Author details

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.

"This ORCID iD identifies the author of this article:" 0000-0003-0982-2150
Tu Lu

Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
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.

"This ORCID iD identifies the author of this article:" 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.

Copyright

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.