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

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Abstract

Polycomb Repressive Complex 2 (PRC2) catalyzes the mono-, di-, and trimethylation of histone protein H3 on lysine 27 (H3K27), which is strongly associated with transcriptionally silent chromatin. The functional core of PRC2 is highly conserved in animals and consists of four subunits. One of these, SUZ12, has not been identified in the genetic model Caenorhabditis elegans, whereas C. elegans PRC2 contains the clade-specific MES-3 protein. Through unbiased sensitive sequence similarity searches complemented by high-quality structure predictions of monomers and multimers, we here demonstrate that MES-3 is a highly divergent ortholog of SUZ12. MES-3 shares protein folds and conserved residues of key domains with SUZ12 and is predicted to interact with core PRC2 members similar to SUZ12 in human PRC2. Thus, in agreement with previous genetic and biochemical studies, we provide evidence that C. elegans contains a diverged yet evolutionary conserved core PRC2, like other animals.

Original languageEnglish
Article number104633
Pages (from-to)1-10
Number of pages9
JournaliScience
Volume25
Issue number7
DOIs
Publication statusPublished - 15 Jul 2022

Bibliographical note

Funding Information:
We would like to thank Danny Hancock for constructing the phylogenetic profiles of PRC2 core members. BS acknowledges funding via the VICI research program, project number 016.160.638, which is financed by the Dutch Research Council (NWO). SvdH contributed to this publication as part of project Single Cell Analysis of Animal Development, with project number 2019.017 of the research program OCENW GROOT/XL, which is also financed by NWO. B.S. S.v.d.H. and M.F.S. conceived the study, performed the experiments, analyzed the data, and drafted the manuscript. The authors declare no competing interests.

Funding Information:
We would like to thank Danny Hancock for constructing the phylogenetic profiles of PRC2 core members. BS acknowledges funding via the VICI research program, project number 016.160.638, which is financed by the Dutch Research Council ( NWO ). SvdH contributed to this publication as part of project Single Cell Analysis of Animal Development, with project number 2019.017 of the research program OCENW GROOT/XL, which is also financed by NWO.

Publisher Copyright:
© 2022 The Author(s)

Keywords

  • 3days reconstruction of protein
  • Biochemistry
  • Bioinformatics
  • protein
  • sequence homology

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