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

ABSTRACT: 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.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE100652 | GEO | 2017/12/08

SECONDARY ACCESSION(S): PRJNA392422

REPOSITORIES: GEO

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Genome-wide maps of chromatin structure in wild-type and nanos mutant primordial germ cells in C. elegans

Project description: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.

2017-12-05 | GSE100651 | GEO

Maternal H3K36 and H3K27 HMTs protect germline development via regulation of the transcription factor LIN-15B

Project description:Maternally synthesized products play critical roles in development of offspring. A premier example is the C. elegans H3K36 methyltransferase MES-4, which is essential for germline survival and development in offspring. How maternal MES-4 protects the germline is not well understood, but its role in H3K36 methylation hinted that it may regulate gene expression in Primordial Germ Cells (PGCs). We tested this hypothesis by profiling transcripts from nascent germlines (PGCs and their descendants) dissected from wild-type and mes-4 mutant (lacking maternal and zygotic MES-4) larvae. mes-4 nascent germlines displayed down-regulation of some germline genes, up-regulation of some somatic genes, and dramatic up-regulation of hundreds of genes on the X chromosome. We demonstrated that up-regulation of 1 or more genes on the X is the cause of germline death by generating and analyzing mes-4 mutants that inherited different endowments of X chromosome(s). Intriguingly, removal of the THAP transcription factor LIN-15B from mes-4 mutants reduced X mis-expression and prevented germline death. lin-15B is X-linked and mis-expressed in mes-4 PGCs, identifying it as a critical target for MES-4 repression. The above findings extend to the H3K27 methyltransferase MES-2/3/6, the C. elegans version of Polycomb Repressive Complex 2. We propose that maternal MES-4 and PRC2 cooperate to protect germline survival by preventing synthesis of germline-toxic products encoded by genes on the X chromosome, including the key transcription factor LIN-15B.

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

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Project description:Investigation of whole genome gene expression level changes in nanos(RNAi) Schmidtea mediterranea, compared to control animals. nanos(RNAi) animals are devoid of germ cells The samples analyzed in this study are further described in Wang, Y., Stary, JM., Wilhelm, JE. and Newmark, PA. 2010. A eight chip study using total RNA recovered from asexual nanos(RNAi), asexual control, juvenile sexual nanos(RNAi), and juvenile sexual control animals. Each chip measures the expression level of 16,797 ESTs from S. mediterranea with 10 60-mer probe pairs (PM/MM) per gene, with two-fold technical redundancy.

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