Reference - Detail
| RRC ID | 84158 |
|---|---|
| Author | Carvalho CA, Abu-Shach UB, Raju A, Vershinin Z, Levy D, Boxem M, Broday L. |
| Title | SUMO-mediated regulation of H3K4me3 reader SET-26 controls germline development in C. elegans. |
| Journal | PLoS Biol |
| Abstract |
Sumoylation is a posttranslational modification essential for multiple cellular functions in eukaryotes. ULP-2 is a conserved SUMO protease required for embryonic development in Caenorhabditis elegans. Here, we revealed that ULP-2 controls germline development by regulating the PHD-SET domain protein, SET-26. Specifically, loss of ULP-2 results in sterility and a progressive elevation of global protein sumoylation. In the germline of ulp-2 null mutant, meiosis is arrested at the diplotene stage and the cells in the proximal germline acquire a somatic fate. Germline RNAseq analysis revealed the down-regulation of numerous germline genes in ulp-2 mutants, whereas somatic gene expression is up-regulated. To determine the key factors that are regulated by ULP-2, we performed a yeast two-hybrid screen and identified the histone methylation reader, SET-26 as a ULP-2 interacting protein. Loss of SET-26 enhanced the sterility of ulp-2 mutant animals. Consistently, SET-26 is sumoylated and its sumoylation levels are regulated by ULP-2. Moreover, we detected a reduction in H3K4 tri-methylation (H3K4me3) histone levels bound to SET-26 in the ulp-2 mutant background suggesting a dependence of this histone reader on balanced sumoylation. Finally, a comparative proteomics screen between WT and ulp-2 loss of activity identified the predicted methyltransferase SET-27 as a ULP-2-dependent SET-26-associated protein. SET-27 knockout genetically interacts with ULP-2 in the germline, but not with SET-26. Taken together, we revealed a SUMO protease/H3K4me3 histone reader axis which is required for the maintenance and regulation of germline development. |
| Volume | 23(1) |
| Pages | e3002980 |
| Published | 2025-1-1 |
| DOI | 10.1371/journal.pbio.3002980 |
| PII | PBIOLOGY-D-24-00826 |
| PMID | 39761316 |
| PMC | PMC11703099 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Gene Expression Regulation, Developmental Germ Cells* / metabolism Histones* / metabolism Meiosis / genetics Methylation Mutation Protein Processing, Post-Translational Sumoylation* |
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| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm3505 tm2467 tm4083 tm3526 tmC6 |