Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells. Restricts the expression of neuronal genes by associating with two distinct corepressors, SIN3A and RCOR1, which in turn recruit histone deacetylase to the promoters of REST-regulated genes. Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier. Transcriptional repression by REST-CDYL via the recruitment of histone methyltransferase EHMT2 may be important in transformation suppression. Represses the expression of SRRM4 in non-neural cells to prevent the activation of neural-specific splicing events and to prevent production of REST isoform 3. Repressor activity may be inhibited by forming heterodimers with isoform 3, thereby preventing binding to NRSE or binding to corepressors and leading to derepression of target genes. Also maintains repression of neuronal genes in neural stem cells, and allows transcription and differentiation into neurons by dissociation from RE1/NRSE sites of target genes. Thereby is involved in maintaining the quiescent state of adult neural stem cells and preventing premature differentiation into mature neurons. Plays a role in the developmental switch in synaptic NMDA receptor composition during postnatal development, by repressing GRIN2B expression and thereby altering NMDA receptor properties from containing primarily GRIN2B to primarily GRIN2A subunits. Acts as a regulator of osteoblast differentiation. Key repressor of gene expression in hypoxia; represses genes in hypoxia by direct binding to an RE1/NRSE site on their promoter regions. May also function in stress resistance in the brain during aging; possibly by regulating expression of genes involved in cell death and in the stress response. Repressor of gene expression in the hippocampus after ischemia by directly binding to RE1/NRSE sites and recruiting SIN3A and RCOR1 to promoters of target genes, thereby promoting changes in chromatin modifications and ischemia-induced cell death. After ischemia, might play a role in repression of miR-132 expression in hippocampal neurons, thereby leading to neuronal cell death. Negatively regulates the expression of SRRM3 in breast cancer cell lines.; Binds to the 3' region of the neuron-restrictive silencer element (NRSE), with lower affinity than full-length REST isoform 1. Exhibits weaker repressor activity compared to isoform 1. May negatively regulate the repressor activity of isoform 1 by binding to isoform 1, thereby preventing its binding to NRSE and leading to derepression of target genes. However, in another study, does not appear to be implicated in repressor activity of a NRSE motif-containing reporter construct nor in inhibitory activity on the isoform 1 transcriptional repressor activity. Post-transcriptional inactivation of REST by SRRM4-dependent alternative splicing into isoform 3 is required in mechanosensory hair cells in the inner ear for derepression of neuronal genes and hearing.

1. our study suggests that NRSF is associated with the progression of ovarian cancer, and NRSF may be a valuable early detection marker of ovarian cancer PMID: 30391650
2. genome-wide scan identified significant evidence for linkage (maximum LOD) score = 4.67 at theta = 0 for D4S398) to markers in a 5.7-cM interval on chromosome 4q12-13.1. The DFNA27 interval spans 8.85 Mb & includes at least 61 predicted and 8 known genes. PMID: 18279434
3. Results from a study on gene expression variability markers in early-stage human embryos shows that REST is a putative expression variability marker as well as a differential gene expression marker for the 3-day, 8-cell embryo stage. PMID: 26288249
4. REST rs1277306 single nucleotide polymorphism was significantly associated with cognitive aging among all subjects in an Elderly Taiwanese Population. PMID: 28142142
5. Study identified 204 REST-interacting proteins and carried out a systematic analysis of their interactome. The interaction networks of REST indicated its involvement in biological processes associated with mRNA processing, chromatin organization, and transcription. Also, it suggests a functional links between REST and TRIM28 during neuronal development. PMID: 27976729
6. Although originally aimed to capture REST activity, REST score was found to be a prognostic factor for overall survival. Further, cell lines with enhanced REST activity was found to be more sensitive to IGF1R, VEGFR and ABL inhibitors. PMID: 27698411
7. Findings have identified REST as a key regulator underlying gene repression and cellular adaptation in hypoxia. PMID: 27531581
8. these findings reveal a role for REST-associated G9a and histone H3K9 methylation in the repression of USP37 expression in medulloblastoma. Reactivation of USP37 by G9a inhibition has the potential for therapeutic applications in REST-expressing medulloblastomas PMID: 28483947
9. Low REST expression is associated with prostate cancer. PMID: 27034167
10. High REST expression is associated breast cancer. PMID: 27004407
11. Findings indicate that RE1 silencing transcriptional factor (REST) regulates its miR-124 and mir-203 gene and suggest how REST maintains oncogenic competence in glioblastoma (GBM)stem cells. These mechanisms could potentially be utilized to block REST-mediated GBM tumorigenesis. PMID: 28040710
12. findings indicate that SCYL1 does not contribute to REST turnover and thus do not support a previous study suggesting a role for SCYL1 in mediating REST degradation PMID: 28570664
13. the consequences of germline final-exon-truncating mutations in REST for organismal development and the association with the Hereditary gingival fibromatosis phenotype. PMID: 28686854
14. the mechanisms of inhibition of the small-molecule drugs 4SC-202 and SP2509 were analyzed. These drugs interfered with the viability of medulloblastoma cells, where REST/NRSF has been implicated in cancer pathogenesis. Thus, a resource for molecular REST/NRSF studies and drug development has been established. PMID: 28218430
15. Induced REST expression is capable of attenuating invasion ability of breast cancer cells. PMID: 27697091
16. Expressions of REST and RCOR1 genes may downregulate SYN1 expression in gliomas. PMID: 27685921
17. REST represses transcription of HIF-1alpha in prolonged hypoxia, thus contributing to the resolution of the HIF-1alpha response. PMID: 26647819
18. A role was determined for the NRSF-BDNF pathway in the modulation of cognitive function in patients with newly diagnosed epilepsy. PMID: 26708060
19. The splicing of REST by SRRM4 could promote the neuroendocrine phenotype in CRPC. PMID: 26071481
20. Mutations in the transcriptional repressor REST predispose to Wilms tumor. PMID: 26551668
21. a new role for REST in regulation of growth and early differentiation decisions in human embryonic stem cells. PMID: 26690059
22. TSPYL2 is an essential component of the REST/NRSF transcriptional complex for TGFbeta signaling activation PMID: 25613376
23. Cultured astrocytes gradually became refractory to reprogramming, in part by the repressor REST preventing Neurog2 from binding to the NeuroD4 promoter. PMID: 26119235
24. identified and validated a novel promoter of the MIR137 gene adjacent to miR-137 itself which can direct the expression of distinct mRNA isoforms encoding miR-137; internal promoter is regulated by repressor element-1 silencing transcription factor (REST) PMID: 25154622
25. Resveratrol via SIRT1/c-Jun downregulates REST mRNA and protein in SH-SY5Y cells. PMID: 26307266
26. Results demonstrate that REST regulates AF1q gene transcription through direct binding at -383 to -363 bp of AF1q promoter. PMID: 26341630
27. The results imply that NRSF/REST plays an important role in the survival of oral cancer cells by regulating the mTOR signaling pathway. PMID: 25524378
28. pioglitazone can inhibit proliferation and induce apoptosis of glioma cell in vitro, which may be mediated by down-regulating REST mRNA level but not by inducing alternative splicing of REST pre-mRNA PMID: 26003726
29. data support the notion of REST presence in human brain neurones and glial cells and indicate the importance of developing compounds able to restore REST-regulated transcription of neuronal genes in Huntington's disease. PMID: 24634989
30. loss of REST induces a pathogenic program that works through the type 1 insulin-like growth factor receptor/insulin receptor substrate 1 pathway. PMID: 26100015
31. The results demonstrate that there is substantial rewiring of human and mouse REST cistromes, and that REST may have human-specific roles in brain development and functions. PMID: 25990720
32. Results indicate that neuron-restrictive silencer factor plays an important role as a repressor of VGF gene regulation in neuroblastoma cells through a mechanism that is dependent on VGF-neuron-restrictive silencer element PMID: 25569790
33. TRF2-mediated counterbalance between hREST4 and REST is vital for both the generation and maintenance of neural progenitor cells PMID: 24740933
34. The STP-REST axis is a molecular driver of human triple-negative breast cancer subtype. PMID: 25453754
35. Assessment of REST-N50 and DOPEY1v2 may prove useful in diagnostic blood tests of breast cancer. REST-N50 shows a high potential as a blood biomarker for evaluating the effectiveness of therapy in the neoadjuvant setting. PMID: 25424701
36. REST variant is associated with slower hippocampal atrophy in MCI/AD. PMID: 25559091
37. REST represses PDYN expression in SH-SY5Y cells and the adult human brain and may have implications for mental health and brain/mental disorders. PMID: 25220237
38. REST is targeted to the HAR1 locus by specific DNA regulatory motifs, resulting in potent transcriptional repression. PMID: 20179156
39. the crucial regulatory function of NRSF in the heart and its importance for maintaining normal cardiac integrity. [review] PMID: 24126098
40. findings show that nSR100 plays a role in the alternative splicing of REST in small cell lung cancer (SCLC); study provides new insight into the role of nSR100 in the expression of sREST, possibly in the pathogenesis of SCLC PMID: 23928058
41. The transcriptional repressor REST binds to an RE-1 element in the STAT1 repressor region and in doing so represses transcription from the STAT1 gene regulatory region in melanoma cells lines. PMID: 23598529
42. positive interaction between REST activity and miR-124a using a luciferase-binding assay and we correlated the reciprocal expression of REST and miR-124a in our clinical cohort PMID: 24068568
43. REST levels during ageing are closely correlated with cognitive preservation and longevity; the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain PMID: 24670762
44. Inhibition of REST suppressed tumor growth, inhibited pericyte marker expression, and increased tumor hypoxia and apoptosis PMID: 24415532
45. Results demonstrate that REST modulates androgen receptor actions in prostate epithelia and that REST expression is negatively correlated with disease recurrence after prostatectomy. PMID: 24163104
46. REST is downregulated in advanced prostate cancer by hypoxia-induced miR-106 cluster genes. PMID: 24135225
47. SNP rs13278062, but not rs1713985 showed nominal evidence of association with AMD in a total of 1273 cases and 1652 controls of Chinese descent. PMID: 24235014
48. Our data show that DN:REST in motor cortex reversed RESTs repressive effects on target genes. PMID: 23151521
49. localization of REST protein on the p85 promoter is inhibited by MDM2 protein. PMID: 23238568
50. The role of REST in the various steps of the expression and function of the dense-core vesicle membrane is critical during development and participates in the dynamic regulation of mature cell physiology. [Review] PMID: 23651552

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Nucleus. Cytoplasm.; [Isoform 2]: Cytoplasm.; [Isoform 3]: Nucleus.; [Isoform 4]: Cytoplasm.

Expressed in neurons of the prefrontal cortex, in hippocampal pyramidal neurons, dentate gyrus granule neurons and cerebellar Purkinje and granule neurons (at protein level). Expressed in dopaminergic neurons of the substantia nigra (at protein level). Ex

HGNC: 9966

OMIM: 600571

KEGG: hsa:5978

STRING: 9606.ENSP00000311816

UniGene: Hs.307836