A conserved role but different partners for the transcriptional corepressor CoREST in fly and mammalian nervous system formation

Julia E. Dallman, Janet Allopenna, Andrew Bassett, Andrew Travers, Gail Mandell

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Identification of conserved proteins that act to establish the neuronal phenotype has relied predominantly on structural homologies of the underlying genes. In the case of the repressor element 1 silencing transcription factor (REST), a central player in blocking the neuronal phenotype in vertebrate non-neural tissue, the invertebrate homolog is absent, raising the possibility that distinct strategies are used to establish the CNS of invertebrates. Using a yeast two-hybrid screen designed specifically to identify functional analogs of REST, we show that Drosophila melanogaster uses a strategy that is functionally similar to, but appears to have evolved independently of, REST. The gene at the center of the strategy in flies encodes the repressor Tramtrack88 (Ttk88), a protein with no discernable homology to REST but that nonetheless is able to interact with the same transcriptional partners. Ttk88 uses the REST corepressor Drosophila CoREST to coordinately regulate a set of genes encoding the same neuronal hallmarks that are regulated by REST in vertebrates. Our findings indicate that repression is an important mechanism for regulating neuronal phenotype across phyla and suggest that co-option of a similar corepressor complex occurred to restrict expression of genes critical for neuronal function to a compartmentalized nervous system.

Original languageEnglish (US)
Pages (from-to)7186-7193
Number of pages8
JournalJournal of Neuroscience
Volume24
Issue number32
DOIs
StatePublished - Aug 11 2004

Keywords

  • CNS
  • Corepressor
  • CoREST
  • Repression
  • REST
  • Tramtrack

ASJC Scopus subject areas

  • Neuroscience(all)

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