Regulation of neuronal traits by a novel transcriptional complex

The transcriptional repressor, REST, helps restrict neuronal traits to neur ons by blocking their expression In nonneuronal cells. To examine the reper cussions of REST expression in neurons, we generated a neuronal cell line t hat expresses REST conditionally. REST expression inhibited differentiation by nerve growth factor, suppressing both sodium current and neurite growth . A novel corepressor complex, CoREST/HDAC2, was shown to be required for R EST repression. In the presence of REST, the CoREST/HDAC2 complex occupied the native Nav1.2 sodium channel gene In chromatin. In neuronal cells that lack REST and express sodium channels, the corepressor complex was not pres ent on the gene. Collectively, these studies define a novel HDAC complex th at is recruited by the C-terminal repressor domain of REST to actively repr ess genes essential to the neuronal phenotype.