Removal of Polycomb Repressive Complex 2 Makes C. elegans Germ Cells Susceptible to Direct Conversion into Specific Somatic Cell Types

Patel, Tulsi; Tursun, Baris; Rahe, Dylan P; Hobert, Oliver

doi:10.1016/j.celrep.2012.09.020

Cited by 113 publications

(135 citation statements)

References 38 publications

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“…The development of different neuronal subtypes can be induced in the C. elegans germline by simultaneous removal of certain chromatin factors and forced expression of master neuronal transcription factors (Tursun et al 2011;Patel et al 2012), highlighting the plasticity of the germline. Notably, other genetic perturbations have been shown to cause C. elegans germ cells to express neuronal and muscle markers, without the need for driving transcription factors.…”

Section: Discussionmentioning

confidence: 99%

Germ Granules Prevent Accumulation of Somatic Transcripts in the AdultCaenorhabditis elegansGermline

et al. 2017

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The germ cells of multicellular organisms protect their developmental potential through specialized mechanisms. A shared feature of germ cells from worms to humans is the presence of nonmembrane-bound, ribonucleoprotein organelles called germ granules. Depletion of germ granules in Caenorhabditis elegans (i.e., P granules) leads to sterility and, in some germlines, expression of the neuronal transgene unc-119::gfp and the muscle myosin MYO-3. Thus, P granules are hypothesized to maintain germ cell totipotency by preventing somatic development, although the mechanism by which P granules carry out this function is unknown. In this study, we performed transcriptome and single molecule RNA-FISH analyses of dissected P granule-depleted gonads at different developmental stages. Our results demonstrate that P granules are necessary for adult germ cells to downregulate spermatogenesis RNAs and to prevent the accumulation of numerous soma-specific RNAs. P granule-depleted gonads that express the unc-119::gfp transgene also express many other genes involved in neuronal development and concomitantly lose expression of germ cell fate markers. Finally, we show that removal of either of two critical P-granule components, PGL-1 or GLH-1, is sufficient to cause germ cells to express UNC-119::GFP and MYO-3 and to display RNA accumulation defects similar to those observed after depletion of P granules. Our data identify P granules as critical modulators of the germline transcriptome and guardians of germ cell fate.

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Section: Discussionmentioning

confidence: 99%

Germ Granules Prevent Accumulation of Somatic Transcripts in the AdultCaenorhabditis elegansGermline

et al. 2017

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“…In Caenorhabditis elegans, spreading of H3K27me3 into adjacent chromatin is prevented by H3K36 methylation (68,69). We therefore asked if methylation of other H3 tail residues affects the distribution of H3K27 methylation in Neurospora.…”

Section: H3k9me3 H3k27me3mentioning

confidence: 99%

Genome-wide redistribution of H3K27me3 is linked to genotoxic stress and defective growth

Basenko

Sasaki

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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H3K9 methylation directs heterochromatin formation by recruiting multiple heterochromatin protein 1 (HP1)-containing complexes that deacetylate histones and methylate cytosine bases in DNA. In Neurospora crassa, a single H3K9 methyltransferase complex, called the DIM-5,-7,-9, CUL4, DDB1 Complex (DCDC), is required for normal growth and development. DCDC-deficient mutants are hypersensitive to the genotoxic agent methyl methanesulfonate (MMS), but the molecular basis of genotoxic stress is unclear. We found that both the MMS sensitivity and growth phenotypes of DCDC-deficient strains are suppressed by mutation of embryonic ectoderm development or Su-(var)3-9; E(z); Trithorax (set)-7, encoding components of the H3K27 methyltransferase Polycomb repressive complex-2 (PRC2). Trimethylated histone H3K27 (H3K27me3) undergoes genome-wide redistribution to constitutive heterochromatin in DCDC- or HP1-deficient mutants, and introduction of an H3K27 missense mutation is sufficient to rescue phenotypes of DCDC-deficient strains. Accumulation of H3K27me3 in heterochromatin does not compensate for silencing; rather, strains deficient for both DCDC and PRC2 exhibit synthetic sensitivity to the topoisomerase I inhibitor Camptothecin and accumulate γH2A at heterochromatin. Together, these data suggest that PRC2 modulates the response to genotoxic stress.

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“…We utilized two pan-neuronal reporter transgenes, unc-119::GFP and unc-33::GFP (Ciosk et al, 2006;Patel et al, 2012;Tursun et al, 2011;Updike et al, 2014) to assay somatic gene expression in the germ line. Both reporters, as expected, were undetectable in wild-type or xnd-1/+ germ lines.…”

Section: Xnd-1 Late Embryos Show Premature Activation Of Transcriptiomentioning

confidence: 99%

A novel germ cell determinant reveals parallel pathways for germ line development inCaenorhabditis elegans

2015

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Despite the central importance of germ cells for transmission of genetic material, our understanding of the molecular programs that control primordial germ cell (PGC) specification and differentiation are limited. Here, we present findings that X chromosome NonDisjunction factor-1 (XND-1), known for its role in regulating meiotic crossover formation, is an early determinant of germ cell fates in Caenorhabditis elegans. xnd-1 mutant embryos display a novel 'one PGC' phenotype as a result of G2 cell cycle arrest of the P 4 blastomere. Larvae and adults display smaller germ lines and reduced brood size consistent with a role for XND-1 in germ cell proliferation. Maternal XND-1 proteins are found in the P 4 lineage and are exclusively localized to the nucleus in PGCs, Z2 and Z3. Zygotic XND-1 turns on shortly thereafter, at the ∼300-cell stage, making XND-1 the earliest zygotically expressed gene in worm PGCs. Strikingly, a subset of xnd-1 mutants lack germ cells, a phenotype shared with nos-2, a member of the conserved Nanos family of germline determinants. We generated a nos-2 null allele and show that nos-2; xnd-1 double mutants display synthetic sterility. Further removal of nos-1 leads to almost complete sterility, with the vast majority of animals without germ cells. Sterility in xnd-1 mutants is correlated with an increase in transcriptional activation-associated histone modification and aberrant expression of somatic transgenes. Together, these data strongly suggest that xnd-1 defines a new branch for PGC development that functions redundantly with nos-2 and nos-1 to promote germline fates by maintaining transcriptional quiescence and regulating germ cell proliferation.

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Removal of Polycomb Repressive Complex 2 Makes C. elegans Germ Cells Susceptible to Direct Conversion into Specific Somatic Cell Types

Cited by 113 publications

References 38 publications

Germ Granules Prevent Accumulation of Somatic Transcripts in the AdultCaenorhabditis elegansGermline

Germ Granules Prevent Accumulation of Somatic Transcripts in the AdultCaenorhabditis elegansGermline

Genome-wide redistribution of H3K27me3 is linked to genotoxic stress and defective growth

A novel germ cell determinant reveals parallel pathways for germ line development inCaenorhabditis elegans

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