Oligomeric Form Of C-Terminal-Binding Protein Coactivates Neurod1-Mediated Transcription

The mechanism underlying transcriptional coactivation by the corepressor C-terminal-binding protein (CtBP) is not established. We previously found that CtBP co-occupies several actively transcribed endocrine genes with the transcription factor NeuroD1 to paradoxically increase transcription by recruiting KDM1A and CoREST. While the importance of the oligomeric form of CtBP for corepression is well established, the role of oligomerization in transcriptional coactivation has received little attention. Here, we examined the importance of the oligomeric state of CtBP for coactivation of NeuroD1-dependent transcription by expressing a CtBP dimerization mutant in cells depleted of endogenous CtBP. Dimerization mutants failed to increase transcription or to associate with KDM1A and CoREST, suggesting that oligomeric, but not monomeric CtBP is required to recruit other proteins needed to activate transcription.