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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 RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.

SUBMITTER: Lee CS

PROVIDER: S-EPMC5734877 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Lee Chih-Yung Sean CS Lu Tu T Seydoux Geraldine G

eLife 20171107

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 act ...[more]

PMID: 29111977

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Project description:modENCODE_submission_2610 This submission comes from a modENCODE project of Michael Snyder. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We are identifying the DNA binding sites for 300 transcription factors in C. elegans. Each transcription factor gene is tagged with the same GFP fusion protein, permitting validation of the gene's correct spatio-temporal expression pattern in transgenic animals. Chromatin immunoprecipitation on each strain is peformed using an anti-GFP antibody, and any bound DNA is deep-sequenced using Solexa GA2 technology. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: OP184(made_by : S Kim description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The LIN-15B::EGFP fusion protein is expressed in the correct lin-15B spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the LIN-15B transcription factor. tags : GFP::3xFlag mutagen : Bombard outcross : 3 genotype : unc119(ed3);wgIs184(lin-15B::TY1 EGFP FLAG;unc119) official name : OP184 ); Developmental Stage: L3; Genotype: unc119(ed3);wgIs184(lin-15B::TY1 EGFP FLAG;unc119); Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage L3; Target gene lin-15B; Strain OP184(made_by : S Kim description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The LIN-15B::EGFP fusion protein is expressed in the correct lin-15B spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the LIN-15B transcription factor. tags : GFP::3xFlag mutagen : Bombard outcross : 3 genotype : unc119(ed3);wgIs184(lin-15B::TY1 EGFP FLAG;unc119) official name : OP184 ); temp (temperature) 20 degree celsius Series_type: CHIP-seq

Dataset Information

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

Publications

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

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