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

Elife. 2017 Nov 7:6: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 RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.

Keywords: C. elegans; C. elegans germline; LIN-15B; Nanos RNA binding protein; cell biology; developmental biology; germ cell fate; primordial germ cells; stem cells; synMuvB.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / biosynthesis*
  • Caenorhabditis elegans Proteins / metabolism*
  • Down-Regulation*
  • Epigenesis, Genetic*
  • Gene Expression Profiling
  • Germ Cells / physiology*
  • Transcription Factors / biosynthesis*

Substances

  • Caenorhabditis elegans Proteins
  • Transcription Factors
  • lin-15B protein, C elegans
  • nos-1 protein, C elegans
  • nos-2 protein, C elegans