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

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...

Full description

Bibliographic Details
Main Authors: Chih-Yung Sean Lee, Tu Lu, Geraldine Seydoux
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-11-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/30201
id doaj-33522224c6064703acae219b60f7ec55
record_format Article
spelling doaj-33522224c6064703acae219b60f7ec552021-05-05T13:55:15ZengeLife Sciences Publications LtdeLife2050-084X2017-11-01610.7554/eLife.30201Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15BChih-Yung Sean Lee0https://orcid.org/0000-0003-0982-2150Tu Lu1https://orcid.org/0000-0002-5697-300XGeraldine Seydoux2https://orcid.org/0000-0001-8257-0493Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United StatesNanos 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 RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.https://elifesciences.org/articles/30201Nanos RNA binding proteinC. elegans germlinesynMuvBgerm cell fateprimordial germ cellsLIN-15B
collection DOAJ
language English
format Article
sources DOAJ
author Chih-Yung Sean Lee
Tu Lu
Geraldine Seydoux
spellingShingle Chih-Yung Sean Lee
Tu Lu
Geraldine Seydoux
Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B
eLife
Nanos RNA binding protein
C. elegans germline
synMuvB
germ cell fate
primordial germ cells
LIN-15B
author_facet Chih-Yung Sean Lee
Tu Lu
Geraldine Seydoux
author_sort Chih-Yung Sean Lee
title Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B
title_short Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B
title_full Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B
title_fullStr Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B
title_full_unstemmed Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B
title_sort nanos promotes epigenetic reprograming of the germline by down-regulation of the thap transcription factor lin-15b
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2017-11-01
description 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 RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.
topic Nanos RNA binding protein
C. elegans germline
synMuvB
germ cell fate
primordial germ cells
LIN-15B
url https://elifesciences.org/articles/30201
work_keys_str_mv AT chihyungseanlee nanospromotesepigeneticreprogramingofthegermlinebydownregulationofthethaptranscriptionfactorlin15b
AT tulu nanospromotesepigeneticreprogramingofthegermlinebydownregulationofthethaptranscriptionfactorlin15b
AT geraldineseydoux nanospromotesepigeneticreprogramingofthegermlinebydownregulationofthethaptranscriptionfactorlin15b
_version_ 1721460468296450048