{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe collection of studies provided here predominantly characterizes the multifaceted roles of the transcriptional repressor REST (RE1‐silencing transcription factor, also known as NRSF) in governing neuronal gene expression, neural stem cell identity, and developmental transitions. In diverse experimental systems—including pluripotent embryonic stem cells, neural progenitors and post‐mitotic neurons—REST is shown to orchestrate the timing of gene activation and repression through dynamic interactions with co‐repressors (such as CoREST), chromatin remodeling complexes, and microRNAs (for example, miR‐124a, miR‐21, and miR‐9). These mechanisms ensure that gene groups essential for neuronal differentiation are maintained in a repressed or “poised” state until the appropriate developmental cues trigger their activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComplementary investigations have extended these observations by exploring how REST‐dependent transcriptional networks intersect with other critical cellular processes. For instance, studies examining the regulation and degradation of ornithine decarboxylase (ODC) reveal how polyamine metabolism and proteasomal degradation pathways contribute to cell proliferation, immune responses, and even neoplastic transformation—mechanisms that are conceptually linked to REST’s role in modulating gene expression under diverse physiological and stress conditions. Moreover, REST-mediated control has been implicated in the modulation of neural excitability, longevity, neurovascular remodeling after ischemia, and even in the reprogramming of non‐neuronal cells towards a neuronal fate."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, investigations into neural circuitry and disease models (including Huntington’s disease, Down syndrome, Parkinson’s disease, and epilepsy) further emphasize REST’s critical contribution to the maintenance of neuronal homeostasis, synaptic plasticity, and the regulation of genes required for proper neurotransmission. These studies also dissect the interplay between REST and additional transcriptional regulators (such as Sp1) that fine-tune the expression of synaptic and cell adhesion molecules, with significant implications for neurodevelopment and neurodegeneration. It is important to note, however, that none of the abstracts in this collection provide any direct evidence for a functional role of OR8H1. Although OR8H1 is traditionally classified as an olfactory receptor and is presumed to participate in odorant detection and signal transduction in the olfactory system, its function is not addressed in these studies, leaving its biological role unelucidated in this context."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Martin A Hoyt, Mingsheng Zhang, Philip Coffino "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin-independent mechanisms of mouse ornithine decarboxylase degradation are conserved between mammalian and fungal cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M211802200"}], "href": "https://doi.org/10.1074/jbc.M211802200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12562772"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12562772"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "David Martin, Thomas Tawadros, Laure Meylan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Critical role of the transcriptional repressor neuron-restrictive silencer factor in the specific control of connexin36 in insulin-producing cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M306861200"}], "href": "https://doi.org/10.1074/jbc.M306861200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14565956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14565956"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mingsheng Zhang, Alasdair I MacDonald, Martin A Hoyt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteasomes begin ornithine decarboxylase digestion at the C terminus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M314043200"}], "href": "https://doi.org/10.1074/jbc.M314043200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15016805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15016805"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Alexander W Bruce, Ian J Donaldson, Ian C Wood, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "RE1 Silencing transcription factor maintains a repressive chromatin environment in embryonic hippocampal neural stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1634/stemcells.2006-0207"}], "href": "https://doi.org/10.1634/stemcells.2006-0207"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17082226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17082226"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Chiara Zuccato, Nikolai Belyaev, Paola Conforti, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "REST maintains self-renewal and pluripotency of embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06863"}], "href": "https://doi.org/10.1038/nature06863"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18362916"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18362916"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Claudia Canzonetta, Claire Mulligan, Samuel Deutsch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DYRK1A-dosage imbalance perturbs NRSF/REST levels, deregulating pluripotency and embryonic stem cell fate in Down syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2008.08.012"}], "href": "https://doi.org/10.1016/j.ajhg.2008.08.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18771760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18771760"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Yuh-Man Sun, Megan Cooper, Sophie Finch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rest-mediated regulation of extracellular matrix is crucial for neural development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0003656"}], "href": "https://doi.org/10.1371/journal.pone.0003656"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18987749"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18987749"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Rory Johnson, Christina Hui-leng Teh, Galih Kunarso, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "REST selectively represses a subset of RE1-containing neuronal genes in mouse embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.028548"}], "href": "https://doi.org/10.1242/dev.028548"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19201947"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19201947"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Aude-Marie Lepagnol-Bestel, Agnes Zvara, Gilles Maussion, et al. 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