RE1-silencing transcription factor (REST)

RE1-silencing transcription factor (REST) is a Kruppel-type zinc finger transcription factor that acts as a master regulator of neuronal gene repression in non-neuronal cells and neural progenitors[1][3][6]. It binds to the RE1/NRSE (neuron-restrictive silencer element) DNA motif in target gene promoters, recruiting cofactors such as CoREST, mSin3A, HDACs, G9a, MECP2, and other chromatin modifiers to establish repressive chromatin, leading to transcriptional silencing[3][6][7]. REST is highly expressed in stem and progenitor cells and represses a broad array of neural genes, thus maintaining non-neuronal identity and modulating neurogenesis[7]. In mature neurons, REST is generally quiescent but can be upregulated in response to cellular stress (e.g., ischemia, seizures) and is implicated in neuronal injury or death in neurodegenerative and ischemic conditions[1][7]. Defective or aberrant REST function is associated with various cancers and several neurodegenerative disorders, underlining its importance as a disease-modifying and potentially therapeutic target[1][2].

Other names

Neuron-restrictive silencer factorNRSFX2 box repressorNeural-restrictive silencer factorDFNA27GINGF5HGF5WT6RE1 silencing transcription factorneuron-restrictive silencer factorrepressor binding to the X2 boxREST4

Inhibition of chromatin remodeling and transcriptional repression (e.g., HDAC inhibition counteracts REST-mediated gene silencing); RNA interference (RNAi) or dominant-negative (dn) REST proteins to block REST function