A conserved role but different partners for the transcriptional corepressor CoREST in fly and mammalian nervous system formation.
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.
Howard Hughes Medical Institute, State University of New York, Stony Brook, Stony Brook, New York 11794, USA.
Julia E
JE
Dallman
Janet
J
Allopenna
Andrew
A
Bassett
Andrew
A
Travers
Gail
G
Mandel
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000196:embryology*; D056970:Co-Repressor Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007814:Larva; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*; D020798:Two-Hybrid System Techniques; D000099229:RE1-Silencing Transcription Factor
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C579421:CoREST protein, Drosophila; C121019:RCOR1 protein, human; C485650:Rcor2 protein, mouse; C075878:ttk protein, Drosophila