A developmental role for the chromatin‑regulating CoREST complex in the cnidarian Nematostella vectensis
Metadatos
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BMC
Materia
Evolution Chromatin modification Gene regulation Development CoREST Lsd1 KDM1A Cnidaria
Fecha
2022-08-23Referencia bibliográfica
Gahan, J.M... [et al.]. A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis. BMC Biol 20, 184 (2022). [https://doi.org/10.1186/s12915-022-01385-1]
Patrocinador
University of Bergen; Research Council of Norway 251185/F20; Sars Centre core budget; Research Council of Norway INFRASTRUKTUR program 295910Resumen
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.