Chromatin reprogramming in primordial germ cells requires Nanos-dependent down-regulation of the synMuvB transcription factor LIN-15B

The Nanos family of RNA-binding proteins has been implicated in the specification of primordial germ cells (PGCs) in a wide range of metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of PGCs lacking the nanos homologues nos-1 and nos-2 in C. elegans using cell sorting and RNA-seq. nos-1nos-2 PGCs fail to silence hundreds of genes normally expressed in oocytes and somatic cells, a phenotype reminiscent of PGCs lacking the repressive PRC2 complex. The nos-1nos-2 phenotype depends on LIN-15B, a broadly expressed synMuvB class transcription factor known to antagonize PRC2 activity in somatic cells. LIN-15B is maternally-inherited by all embryonic cells and is down-regulated specifically in PGCs in a nos-1nos-2-dependent manner. Consistent with LIN-15B being a critical target of Nanos regulation, inactivation of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These studies demonstrate a central role for Nanos in reprogramming the transcriptome of primordial germ cells away from an oocyte/somatic fate by down-regulating an antagonist of PRC2 activity. Overall design: 30 RNA-seq samples are inclued in this study. These include PGC transcriptomes from wild-type, nos-1(gv5)nos-2(RNAi), mes-2(RNAi), mes-4(RNAi), nos-1(gv5)nos-2(RNAi);lin15-B(RNAi) and biological replicates.

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Lee CS, Putnam A, Lu T, He S, Ouyang JPT, Seydoux G