Caenorhabditis elegans MES-3 is a highly divergent ortholog of the canonical PRC2 component SUZ12

Snel, Berend; Heuvel, Sander van den; Seidl, Michael

doi:10.1016/j.isci.2022.104633

Cited by 7 publications

(14 citation statements)

References 43 publications

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“…We only found a P. pacificus ortholog of MES-6 that is highly truncated, likely a non-functional pseudogene, and a P. mayeri ortholog of MES-2. C. elegans MES-3 formed an isolated orthogroup, separate from all other SUZ12 orthologs (consistent with previous reports that MES-3 and SUZ12 are highly diverged orthologs; Snel et al 2022); neither orthogroup included any Pristionchus species. Based on these results, we wondered if PRC2 was lost in multiple Pristionchus nematodes.…”

Section: Resultssupporting

confidence: 89%

“…In both humans and C. elegans, the PRC2 complex contains three core proteins, each required for catalytic activity: the enzymatic component MES-2/EZH2 and two cofactors MES-3/SUZ12 and MES-6/EED (Fig. 4D) (Jiao and Liu 2015; Ahringer and Gasser 2018; Snel et al 2022). We first examined our previous orthogroup phylogenies for each of these three proteins to see if we could identify orthologs in P. pacificus, as well as in the related Pristionchus nematodes P. exspectatus and P. mayeri (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Characterization of thePristionchus pacificus“epigenetic toolkit” reveals the evolutionary loss of the histone methyltransferase complex PRC2

Brown,

Meiborg,

Franz-Wachtel

et al. 2023

Preprint

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Comparative approaches have revealed both divergent and convergent paths to achieving shared developmental outcomes. Thus, only through assembling multiple case studies can we understand biological principles. Yet, despite appreciating the conservation – or lack thereof – of developmental networks, the conservation of epigenetic mechanisms regulating these networks is poorly understood. The nematodePristionchus pacificushas emerged as a model system of plasticity and epigenetic regulation as it exhibits a bacterivorous or omnivorous morph depending on its environment. Here, we determined the “epigenetic toolkit” available toP. pacificusas a resource for future functional work on plasticity, and as a comparison withC. elegansto investigate the conservation of epigenetic mechanisms. Broadly, we observed a similar cast of genes with putative epigenetic function betweenC. elegansandP. pacificus. However, we also found striking differences. Most notably, the histone methyltransferase complex PRC2 appears to be missing inP. pacificus.We described the deletion/pseudogenization of the PRC2 genesmes-2andmes-6and concluded that both were lost in the last common ancestor ofP. pacificusand a related speciesP. arcanus.Interestingly, we observed the enzymatic product of PRC2 (H3K27me3) by mass spectrometry and immunofluorescence, suggesting that a currently unknown methyltransferase has been co-opted for heterochromatin silencing. Altogether, we have provided an inventory of epigenetic genes inP. pacificusto enable reverse-genetic experiments related to plasticity, and in doing so have described the first loss of PRC2 in a multicellular organism.

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Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Characterization of thePristionchus pacificus“epigenetic toolkit” reveals the evolutionary loss of the histone methyltransferase complex PRC2

Brown,

Meiborg,

Franz-Wachtel

et al. 2023

Preprint

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“…In C. elegans , the X chromosomes in XX hermaphrodites and XO males are globally “silenced” during most stages of C. elegans germ cell development through the combined activity of the MES (maternal effect sterile) proteins. MES-2/3/6 are homologs of PRC2 (Gaydos et al, 2014; Bender et al, 2006; Snel et al, 2022) and deposit repressive H3K27me3 (Bender et al, 2006; Gaydos et al, 2014). MES-4 instead deposits the activating mark H3K36me3 on germline expressed autosomal genes and antagonizes H3K27me3, leading to its concentration on the X (Gaydos et al, 2014; Bender et al, 2006).…”

Section: Resultsmentioning

confidence: 99%

SIN3 acts in distinct complexes to regulate the germline transcriptional program inC. elegans

Caron

Robert

Gely

et al. 2023

Preprint

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The SIN3 transcriptional coregulator influences gene expression through multiple interactions that include histone deacetylases (HDACs). Haploinsufficiency and mutations in SIN3 are the underlying cause of Witteveen-Kolk syndrome and related intellectual disability (ID)/autism syndromes, emphasizing its key role in development. However, little is known about the diversity of its interactions and functions in developmental processes. Here we show that loss of SIN-3, the single SIN3 homologue in Caenorhabditis elegans, results in maternal effect sterility associated with deregulation of the germline transcriptome, including desilencing of X-linked genes. We identify at least two distinct SIN3 complexes containing specific HDACs, and show that they differentially contribute to fertility. Single cell smFISH reveals that in sin-3 mutants, the X chromosome becomes re-expressed prematurely and in a stochastic manner in individual germ cells. Furthermore, we identify histone residues whose acetylation increases in the absence of SIN3. Together, this work provides a powerful framework for the in vivo study of SIN3 and associated proteins.

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“…Contrary to the general believe that fungi have lost PRC1, we uncovered PRC1 orthologs in multiple deep branching fungal species. Furthermore, we identified orthologs that had previously gone undetected because of their significant sequence divergence, such as EED in ciliates and SUZ12 orthologs in Cryptococcus neoformans and Caenorhabditis elegans (Snel et al 2022). We expect that increasingly sensitive techniques will uncover additional species harboring divergent Polycomb orthologs or other, currently unknown, subunits.…”

Section: Discussionmentioning

confidence: 99%

“…Like EED, SUZ12 was also found to be highly divergent in various species, e.g., a recent study demonstrated that MES-3 in Caenorhabditis elegans is a diverged SUZ12 ortholog rather than a Caenorhabditis elegans specific addition to PRC2 (Snel et al 2022). The N-terminus of SUZ12 in animals contains five motifs: a zinc-finger binding (ZnB), WD-domain binding 1 (WDB1), C2 domain, zinc finger (Zn), and WD-domain binding 2 (WDB2) (Fig.…”

Section: Evidence For the Presence Of Prc2 In Lecamentioning

confidence: 99%

Uncoupled evolution of the Polycomb system and deep origin of non-canonical PRC1

Potter

Raas

Seidl

et al. 2023

Preprint

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Polycomb group (PcG) proteins modulate chromatin states to silence gene transcription in plants and animals. Most PcG proteins function as part of distinct multi-subunit Polycomb repressive complexes (PRCs). Gene repression by the Polycomb system involves chromatin compaction by canonical PRC1 (cPRC1), mono-ubiquitylation of histone H2A (H2Aub1) by non-canonical PRC1 (ncPRC1) and tri methylation of histone H3K27 (H3K27me3) by PRC2. Prevalent models for Polycomb repression emphasize a tight functional coupling between PRC1 and PRC2. However, whether this paradigm indeed reflects the evolution and functioning of the Polycomb system remains unclear. Here, we examined the relationship between cPRC1, ncPRC1 and PRC2 through a comprehensive analysis of their presence and evolution across the entire eukaryotic tree of life. We show that both PRC1 and PRC2 were present in the Last Eukaryotic Common Ancestor (LECA), but that their subsequent evolution is uncoupled. The identification of orthologs for ncPRC1-defining subunits in unicellular relatives of animals and of fungi suggests that the origin of ncPRC1 predates that of cPRC1, and we develop a scenario for the evolution of cPRC1 from ncPRC1. Our results demonstrate the independent evolution and function of PRC1 and PRC2 and show that crosstalk between these complexes is a secondary development in evolution.

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Caenorhabditis elegans MES-3 is a highly divergent ortholog of the canonical PRC2 component SUZ12

Cited by 7 publications

References 43 publications

Characterization of thePristionchus pacificus“epigenetic toolkit” reveals the evolutionary loss of the histone methyltransferase complex PRC2

Characterization of thePristionchus pacificus“epigenetic toolkit” reveals the evolutionary loss of the histone methyltransferase complex PRC2

SIN3 acts in distinct complexes to regulate the germline transcriptional program inC. elegans

Uncoupled evolution of the Polycomb system and deep origin of non-canonical PRC1

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