synMuv B proteins antagonize germline fate in the intestine and ensure <i>C. elegans</i> survival

Petrella, Lisa N.; Wang, Qianqian; Spike, Caroline A.; Rechtsteiner, Andreas; Reinke, V; Strome, Susan

doi:10.1242/dev.059501

Cited by 89 publications

(261 citation statements)

References 49 publications

(72 reference statements)

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“…To test for somatic expression of P-granule and synaptonemal-complex proteins in daf-2 mutants, we immunostained daf-2 L1 larvae for the P-granule protein PGL-3 and the meiotic protein HTP-3. Although robust PGL-3 and HTP-3 staining was observed in somatic cells of synMuv B mutants (e.g., lin-13), which are known to ectopically express a germ-line program in their soma (11)(12)(13), PGL-3 and HTP-3 were not detected in somatic cells of daf-2(e1368) or daf-2(e1370) worms (Fig. 1A).…”

Section: Daf-2 Mutants Do Not Detectably Express Germ-line Proteins Imentioning

confidence: 99%

“…Treatment of daf-2 young adults with mes-4 RNAi was also reported to modestly decrease lifespan (9). Based on analysis of synMuv B mutants (see below), MES-4 promotes expression of a germ-line program in somatic cells (11)(12)(13). Importantly, MES-4 affects germ-line development and expression of germ-line genes in the soma of synMuv B mutants in a maternal-effect manner (13,23).…”

Section: Daf-2 Mutants Do Not Detectably Express Germ-line Proteins Imentioning

confidence: 99%

“…A striking example of a soma-toward-germ transformation is seen in the synMuv (synthetic Multivulva) B mutants (11)(12)(13). The synMuv B genes encode chromatin regulators that broadly function in gene repression.…”

mentioning

confidence: 99%

“…As a result of ectopic germ-line gene expression in the soma, synMuv B mutants arrest as larvae when grown at elevated temperatures. Notably, ectopic germ-line gene expression and larval arrest can be suppressed by inactivating the germ-line transcriptional program (13).…”

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confidence: 99%

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Reevaluation of whether a soma–to–germ-line transformation extends lifespan in Caenorhabditis elegans

Knutson

Rechtsteiner

Strome

2016

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

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The germ lineage is considered to be immortal. In the quest to extend lifespan, a possible strategy is to drive germ-line traits in somatic cells, to try to confer some of the germ lineage's immortality on the somatic body. Notably, a study in Caenorhabditis elegans suggested that expression of germ-line genes in the somatic cells of long-lived daf-2 mutants confers some of daf-2's long lifespan. Specifically, mRNAs encoding components of C. elegans germ granules (P granules) were up-regulated in daf-2 mutant worms, and knockdown of individual P-granule and other germ-line genes in daf-2 young adults modestly reduced their lifespan. We investigated the contribution of a germ-line program to daf-2's long lifespan and also tested whether other mutants known to express germ-line genes in their somatic cells are long-lived. Our key findings are as follows. (i) We could not detect P-granule proteins in the somatic cells of daf-2 mutants by immunostaining or by expression of a P-granule transgene. (ii) Whole-genome transcript profiling of animals lacking a germ line revealed that germ-line transcripts are not up-regulated in the soma of daf-2 worms compared with the soma of control worms. (iii) Simultaneous removal of multiple P-granule proteins or the entire germ-line program from daf-2 worms did not reduce their lifespan. (iv) Several mutants that robustly express a broad spectrum of germ-line genes in their somatic cells are not long-lived. Together, our findings argue against the hypothesis that acquisition of a germ-cell program in somatic cells increases lifespan and contributes to daf-2's long lifespan.germ line | aging | C. elegans | daf-2 | P granules G erm and soma are the two most fundamentally different cell types found in multicellular organisms (1). Germ cells are totipotent and constitute the only immortal lineage, capable of generating entire new organisms generation after generation, whereas somatic cells differentiate into specialized cell types and are mortal, senescing and dying each generation. Maintaining the proper identity of these cell types is essential for propagation of species, and molecular barriers at both the transcriptional and translational levels have evolved to ensure the germ-soma distinction (1). Removal of these barriers in germ cells can lead to both expression of somatic factors and sterility (2-4), whereas removal of these barriers in somatic cells is associated with reentry into the cell cycle and cancer (5, 6). Despite these barriers, it is unknown whether some cell types can tolerate partial fate switching and perhaps adopt traits of other cell types to benefit the organism.An attractive possibility is that acquisition of a germ-cell program by the somatic body can capture some of the immortality of the germ lineage and extend lifespan (7,8). Indeed, a study in Caenorhabditis elegans supports that possibility (9). In C. elegans, inhibition of the insulin-like signaling pathway by a mutation in daf-2 doubles lifespan through activation of the FOXO transcription factor DAF-16...

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Section: Daf-2 Mutants Do Not Detectably Express Germ-line Proteins Imentioning

confidence: 99%

Section: Daf-2 Mutants Do Not Detectably Express Germ-line Proteins Imentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Reevaluation of whether a soma–to–germ-line transformation extends lifespan in Caenorhabditis elegans

Knutson

Rechtsteiner

Strome

2016

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

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“…Yet, it is of note that misexpression of germline-specific P granule components in the intestine in synMuv B mutants leads to high temperature arrest, a phenotype that is suppressed by global regulators of germline chromatin including the MES-2/3/6 complex. 13 The suppression of xnd-1 meiotic phenotypes by mes-2 and mes-3 14 raises the possibility of a similar consequence for XND-1 misexpression.…”

Section: Introductionmentioning

confidence: 99%

A twist of fate: How a meiotic protein is providing new perspectives on germ cell development

Rana

Yanowitz

2016

Worm

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The molecular pathways that govern how germ line fate is acquired is an area of intense investigation that has major implications for the development of assisted reproductive technologies, infertility interventions, and treatment of germ cell cancers. Transcriptional repression has emerged as a primary mechanism to ensure suppression of somatic growth programs in primordial germ cells. In this commentary, we address how xnd-1 illuminates our understanding of transcriptional repression and how it is coordinated with the germ cell differentiation program. We recently identified xnd-1 as a novel, early determinant of germ cell fates in Caenorhabditis elegans. Our study revealed that XND-1 is maternally deposited into early embryos where it is selectively enriched in the germ lineage and then exclusively found on chromatin in the germ lineage throughout development and into adulthood when it dissociates from chromosomes in late pachytene. This localization is consistent with a range of interesting germ cell defects that suggest xnd-1 is a pivotal determinant of germ cell characteristics. Loss of xnd-1 results in a unique "one PGC (primordial germ cell)" phenotype due to G2 cell cycle arrest of the germline precursor blastomere, P 4 , which predisposes the animal and its progeny for reduced fecundity. The sterility in xnd-1 mutants is correlated with an increase in the transcriptional activationassociated histone modification, dimethylation of histone H3 lysine 4 (H3K4me2), and aberrant expression of somatic transgenes but overlapping roles with nos-2 and nos-1 suggest that transcriptional repression is achieved by multiple redundant mechanisms.

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Epigenetics in C. elegans: Facts and challenges

Wenzel¹,

Palladino²,

Jedrusik-Bode³

2011

Genesis

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Epigenetics is defined as the study of heritable changes in gene expression that are not accompanied by changes in the DNA sequence. Epigenetic mechanisms include histone post-translational modifications, histone variant incorporation, non-coding RNAs, and nucleosome remodeling and exchange. In addition, the functional compartmentalization of the nucleus also contributes to epigenetic regulation of gene expression. Studies on the molecular mechanisms underlying epigenetic phenomena and their biological function have relied on various model systems, including yeast, plants, flies, and cultured mammalian cells. Here we will expose the reader to the current understanding of epigenetic regulation in the roundworm C. elegans. We will review recent models of nuclear organization and its impact on gene expression, the biological role of enzymes modifying core histones, and the function of chromatin-associated factors, with special emphasis on Polycomb (PcG) and Trithorax (Trx-G) group proteins. We will discuss how the C. elegans model has provided novel insight into mechanisms of epigenetic regulation as well as suggest directions for future research.

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synMuv B proteins antagonize germline fate in the intestine and ensure C. elegans survival

Cited by 89 publications

References 49 publications

Reevaluation of whether a soma–to–germ-line transformation extends lifespan in Caenorhabditis elegans

Reevaluation of whether a soma–to–germ-line transformation extends lifespan in Caenorhabditis elegans

A twist of fate: How a meiotic protein is providing new perspectives on germ cell development

Epigenetics in C. elegans: Facts and challenges

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