A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis
Abstract Background Chromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Most chromatin modifiers, however, predate the evolution of animal multicellularity, and how they gained new functions and became integrated into the regulatory netw...
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-022-01385-1 |
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| author | James M. Gahan Lucas Leclère Maria Hernandez-Valladares Fabian Rentzsch |
| author_facet | James M. Gahan Lucas Leclère Maria Hernandez-Valladares Fabian Rentzsch |
| author_sort | James M. Gahan |
| collection | DOAJ |
| description | Abstract Background Chromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Most chromatin modifiers, however, predate the evolution of animal multicellularity, and how they gained new functions and became integrated into the regulatory networks underlying development is unclear. One way this may occur is the evolution of new scaffolding proteins that integrate multiple chromatin regulators into larger complexes that facilitate coordinated deposition or removal of different chromatin modifications. We test this hypothesis by analyzing the evolution of the CoREST-Lsd1-HDAC complex. Results Using phylogenetic analyses, we show that a bona fide CoREST homolog is found only in choanoflagellates and animals. We then use the sea anemone Nematostella vectensis as a model for early branching metazoans and identify a conserved CoREST complex by immunoprecipitation and mass spectrometry of an endogenously tagged Lsd1 allele. In addition to CoREST, Lsd1 and HDAC1/2 this complex contains homologs of HMG20A/B and PHF21A, two subunits that have previously only been identified in mammalian CoREST complexes. NvCoREST expression overlaps fully with that of NvLsd1 throughout development, with higher levels in differentiated neural cells. NvCoREST mutants, generated using CRISPR-Cas9, fail to develop beyond the primary polyp stage, thereby revealing essential roles during development and for the differentiation of cnidocytes that phenocopy NvLsd1 mutants. We also show that this requirement is cell autonomous using a cell-type-specific rescue approach. Conclusions The identification of a Nematostella CoREST-Lsd1-HDAC1/2 complex, its similarity in composition with the vertebrate complex, and the near-identical expression patterns and mutant phenotypes of NvCoREST and NvLsd1 suggest that the complex was present before the last common cnidarian-bilaterian ancestor and thus represents an ancient component of the animal developmental toolkit. |
| first_indexed | 2024-04-14T02:57:45Z |
| format | Article |
| id | doaj.art-3a48def9aeb640eeb8af54067ffd13e6 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-04-14T02:57:45Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-3a48def9aeb640eeb8af54067ffd13e62022-12-22T02:16:01ZengBMCBMC Biology1741-70072022-08-0120111610.1186/s12915-022-01385-1A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensisJames M. Gahan0Lucas Leclère1Maria Hernandez-Valladares2Fabian Rentzsch3Sars International Centre for Marine Molecular Biology, University of BergenSorbonne Université, CNRS, Laboratoire de Biologie du Développement de Villefranche-Sur-Mer (LBDV)Department of Physical Chemistry, University of GranadaSars International Centre for Marine Molecular Biology, University of BergenAbstract Background Chromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Most chromatin modifiers, however, predate the evolution of animal multicellularity, and how they gained new functions and became integrated into the regulatory networks underlying development is unclear. One way this may occur is the evolution of new scaffolding proteins that integrate multiple chromatin regulators into larger complexes that facilitate coordinated deposition or removal of different chromatin modifications. We test this hypothesis by analyzing the evolution of the CoREST-Lsd1-HDAC complex. Results Using phylogenetic analyses, we show that a bona fide CoREST homolog is found only in choanoflagellates and animals. We then use the sea anemone Nematostella vectensis as a model for early branching metazoans and identify a conserved CoREST complex by immunoprecipitation and mass spectrometry of an endogenously tagged Lsd1 allele. In addition to CoREST, Lsd1 and HDAC1/2 this complex contains homologs of HMG20A/B and PHF21A, two subunits that have previously only been identified in mammalian CoREST complexes. NvCoREST expression overlaps fully with that of NvLsd1 throughout development, with higher levels in differentiated neural cells. NvCoREST mutants, generated using CRISPR-Cas9, fail to develop beyond the primary polyp stage, thereby revealing essential roles during development and for the differentiation of cnidocytes that phenocopy NvLsd1 mutants. We also show that this requirement is cell autonomous using a cell-type-specific rescue approach. Conclusions The identification of a Nematostella CoREST-Lsd1-HDAC1/2 complex, its similarity in composition with the vertebrate complex, and the near-identical expression patterns and mutant phenotypes of NvCoREST and NvLsd1 suggest that the complex was present before the last common cnidarian-bilaterian ancestor and thus represents an ancient component of the animal developmental toolkit.https://doi.org/10.1186/s12915-022-01385-1EvolutionChromatin modificationGene regulationDevelopmentCoRESTLsd1 |
| spellingShingle | James M. Gahan Lucas Leclère Maria Hernandez-Valladares Fabian Rentzsch A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis BMC Biology Evolution Chromatin modification Gene regulation Development CoREST Lsd1 |
| title | A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis |
| title_full | A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis |
| title_fullStr | A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis |
| title_full_unstemmed | A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis |
| title_short | A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis |
| title_sort | developmental role for the chromatin regulating corest complex in the cnidarian nematostella vectensis |
| topic | Evolution Chromatin modification Gene regulation Development CoREST Lsd1 |
| url | https://doi.org/10.1186/s12915-022-01385-1 |
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