Repressor element-1 silencing transcription factor (REST)

Repressor element-1 silencing transcription factor (REST), also known as neuron-restrictive silencer factor (NRSF), is a Kruppel-type zinc finger transcription factor that represses genes involved in neuronal differentiation and function by binding to DNA at neuron-restrictive silencer elements (NRSE/RE1)[1][2][3][9]. REST is a master negative regulator of neurogenesis, present at high levels in non-neuronal tissues, and represses neuronal genes while its downregulation is necessary for neuronal development and maturation[1][2][5]. The REST protein exerts its function by recruiting chromatin-modifying enzymes, including histone deacetylases and demethylases, leading to epigenetic silencing of its target genes[1][3][8][9]. REST regulates thousands of target genes, including those encoding for neurotransmitter receptors, synaptic proteins, ion channels, and cell adhesion molecules[2][3]. It plays a role in chromatin plasticity, alternative mRNA splicing, and stress response to hypoxia and ischemia[1][7]. Dysregulation or mutation of REST is implicated in cancer, neurodegenerative conditions (e.g., Huntington's and Alzheimer's diseases), epilepsy, ischemic injury, and other pathologies[1][2][5]. Though not a direct target of current approved drugs, REST-modulating strategies are under research for neuroprotection and cancer therapy[1][2][3][5].

Other names

Neuron-restrictive silencer factor (NRSF)RESTNRSF

Transcriptional repression by recruitment of chromatin-modifying enzymes (e.g., histone deacetylases), epigenetic remodeling, modulation of gene expression through DNA binding at RE1/NRSE sites[1][3][8][9].