{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRE1‐silencing transcription factor (REST), also known as neuron‐restrictive silencer factor (NRSF), functions as a master transcriptional repressor that binds to conserved RE1/NRSE motifs throughout the genome. Genome‐wide mapping studies have revealed that REST directly interacts with thousands of genomic loci to regulate neuronal and non‐neuronal gene networks by recruiting various chromatin remodeling and histone‐modifying complexes. In developing and mature cells, REST mediates cell fate by silencing neuronal genes through associated co‐repressors (e.g., CoREST, Sin3A, HDACs, SCPs, SWI/SNF components) and by orchestrating dynamic epigenetic modifications. Furthermore, REST binding shows intrinsic affinity hierarchies determined by consensus and atypical RE1 motifs, thereby tailoring transcriptional programs to the developmental state and cell type."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nREST is also pivotal in fine‐tuning the cellular response during stress, differentiation and cell cycle progression. Its regulated degradation via ubiquitin ligases (e.g., SCF β‐TRCP) and stabilization by deubiquitylases (e.g., HAUSP) ensure proper timing of neuronal gene derepression during neural differentiation and mitotic checkpoint control. In the context of neurodegenerative disorders, REST is induced during normal aging to repress pro‐apoptotic and stress‐inducing genes, whereas its loss or improper localization is linked to Alzheimer’s, Huntington’s disease and aberrant miRNA/lncRNA expression. Furthermore, dysregulation of REST contributes to tumorigenesis in neural and non‐neural tissues—a dual role in which both loss and aberrant expression (or splicing) have been implicated in medulloblastoma, glioblastoma, breast, lung, prostate and Wilms tumors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical role in repressing neuronal gene transcription, REST governs cellular plasticity, migration and metabolism in both normal physiology and disease. 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