MEP-1 and a Homolog of the NURD Complex Component Mi-2 Act Together to Maintain Germline-Soma Distinctions in C. elegans

Unhavaithaya, Yingdee; Shin, Tae Ho; Miliaras, Nicholas; Lee, Jung-soon; Oyama, Tomoko; Mello, Craig C.

doi:10.1016/s0092-8674(02)01202-3

Cited by 185 publications

(258 citation 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%

“…As another approach to testing whether expression of a germ-line program in somatic cells extends lifespan, we analyzed the synMuv B mutants. synMuv B mutants express in their soma numerous germ-line genes, including genes encoding P-granule components and meiotic factors (11)(12)(13). The degree of germ-line gene expression in somatic cells is strongly influenced by temperature: synMuv B mutant animals grown at high temperatures (e.g., 26°C) have higher levels of ectopic germ-line gene expression than animals grown at lower temperatures (e.g., 20°C) (ref.…”

Section: Synmuv B Mutants Ectopically Express Germ-line Factors But Amentioning

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.…”

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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%

Section: Synmuv B Mutants Ectopically Express Germ-line Factors But Amentioning

confidence: 99%

mentioning

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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“…For example, Caenorhabditis elegans mi‐2 /LET‐418 acts with the transcription factor MEP‐1 to suppress germline fate in somatic cells (Unhavaithaya et al. 2002) and mouse Mi‐2beta suppresses production of erythroid progenitors while promoting myeloid and lymphoid progenitors (Yoshida et al. 2008).…”

Section: Resultsmentioning

confidence: 99%

The NuRD complex componentp66suppresses photoreceptor neuron regeneration in planarians

Vásquez-Doorman

Petersen

2016

Regeneration

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Regeneration involves precise control of cell fate to produce an appropriate complement of tissues formed within a blastema. Several chromatin‐modifying complexes have been identified as required for regeneration in planarians, but it is unclear whether this class of molecules uniformly promotes the production of differentiated cells. We identify a function for p66, encoding a DNA‐binding protein component of the NuRD (nucleosome remodeling and deacetylase) complex, as well as the chromodomain helicase chd4, in suppressing production of photoreceptor neurons (PRNs) in planarians. This suppressive effect appeared restricted to PRNs because p66 inhibition did not influence numbers of eye pigment cup cells (PCCs) and decreased numbers of brain neurons and epidermal progenitors. PRNs from p66(RNAi) animals differentiated with some abnormalities but nonetheless produced arrestin+ projections to the brain. p66 inhibition produced excess ovo+otxA+ PRN progenitors without affecting numbers of ovo+otxA− PCC progenitors, and ovo and otxA were each required for the p66(RNAi) excess PRN phenotype. Together these results suggest that p66 acts through the NuRD complex to suppress PRN production by limiting expression of lineage‐specific transcription factors.

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Nematode (C. elegans), Molecular Biology of

Chisholm

2006

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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MEP-1 and a Homolog of the NURD Complex Component Mi-2 Act Together to Maintain Germline-Soma Distinctions in C. elegans

Cited by 185 publications

References 44 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

The NuRD complex componentp66suppresses photoreceptor neuron regeneration in planarians

Nematode (C. elegans), Molecular Biology of

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