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REST (RE1-silencing transcription factor)

Identity

Other namesNRSF
XBR
HGNC (Hugo) REST
LocusID (NCBI) 5978
Location 4q12
Location_base_pair Starts at 57775079 and ends at 57802010 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note REST/NRSF negatively regulates the transcription of genes containing RE1 sites (Chong et al., 1995; Schoenherr and Anderson, 1995). REST has context dependent roles as both a tumour suppressor and an oncogene (Coulson, 2005).

DNA/RNA

 
  Schematic illustrating REST mRNA and alternative splice variants. The human REST gene is shown (top) illustrating the three main exons (dark blue), an alternative exon (light blue) and one of three alternative 5' non-coding exons (white). The approximate position of sequence encoding eight zinc fingers are illustrated by boxes, these are associated with DNA binding (white) or nuclear import (red). Six alternative mRNAs are illustrated below, the REST reference sequence (NM_005612.3) codes for the major isoform 1. Splice variants described in human *neuroblastoma (Palm et al., 1999) or **SCLC (Coulson et al., 2000) are also shown. REST 1 and REST-5FΔ code for isoform 2 or isoform 4 respectively. The alternative exon in REST-N62, REST-N4 and sNRSF (N50) introduces a premature stop codon and all three transcripts encode isoform 3 (sNRSF/REST4).
Description The REST gene spans 24 kb of genomic DNA. It is composed of: three alternative 5' non-coding exons associated with different gene promoters, three coding exons, an internal alternative exon that is spliced into some neural and disease associated transcripts.
Transcription According to Entrezgene the REST gene encodes a single reference sequence mRNA of 3663 bp (NM_005612.3) that is composed of four exons. However, the literature indicates that at least six different splice variants of REST exist and are associated with neural gene expression and certain disease states.

Protein

 
  Schematic illustrating REST protein and alternative isoforms. Uniprot.org shows the existence of 4 REST isoforms. Isoform 1 is the canonical sequence; it comprises two repression domains (RD1 and RD2), lysine-rich (400-603) and proline-rich (595-815) domains, a DNA binding domain (159-412) of eight zinc fingers (boxes), two nuclear localization signals (shown in red), a phosphodegron (E1009/S1013 or S1027/S1030) and a ninth C-terminal zinc finger (1006-1082). REST can recruit a variety of transcriptional co-repressors through interaction at RD1 or RD2; examples are illustrated including Sin3A (interaction maps to 32-122), Sin3B (43-57) and RCOR1 (1009-1087). Isoform 2 is truncated, retaining only zinc fingers 1-4 and localizes to the cytoplasm. Isoform 3, also called REST4 or sNRSF, is expressed in neuroblastoma and SCLC; it lacks RD2 and has a truncated DNA binding domain, but retains zinc fingers 1-5 and nuclear localization. Isoform 4 has selective deletion of zinc finger 5. (Palm et al., 1999; Coulson et al., 2000; Shimojo et al., 2001).
Description Isoform 1: 1097 amino acids, 122 kDa protein,
Isoform 2: (Δ314-1097), 313 amino acids, 35 kDa protein,
Isoform 3: (Δ330-1097), 329 amino acids, 37 kDa protein,
Isoform 4: (Δ304-326), 1074 amino acids, 119 kDa protein.
Expression REST shows specific expression patterns during development, and exhibits tissue-specific, cell cycle associated or disease dependent expression. This context-dependent expression of REST is regulated through differential transcription, splicing and proteasome-mediated degradation. REST is under expressed in differentiated neuronal tissue, however it plays an essential role during embryogenesis as mice that lack REST die by embryonic day 11.5. Although these mice appear normal until embryonic day 9.5, widespread apoptotic death then results in malformations in the developing nervous system and restricted growth (Chen et al., 1998). In other adult tissues, REST is ubiquitously expressed showing preferential accumulation in tissues of the lymphocytic compartment, including spleen, thymus, peripheral blood lymphocytes, and also in ovary (Scholl et al., 1996).
Localisation REST is predicted to localize to the nucleus, however the literature reports differential localization of some isoforms. REST undergoes nucleocytoplasmic shuttling, its nuclear targeting is dependent on either a classical NLS or zinc finger 5 (Shimojo et al., 2001) and is influenced by association with other proteins such as PRICKLE1 (RILP) (Shimojo and Hersh, 2003), HTT (Zuccato et al., 2003) and DCTN1 (p150-Glued) (Shimojo, 2008). REST may also be recruited to nuclear PML bodies by association with TRF2 (Zhang et al., 2008).
Function REST is a transcriptional repressor with a role in regulating gene expression. It was identified in 1995 as a protein that bound to the repressor element 1 (RE1 or NRSE) motif, primarily located in promoter regions of neuron-specific genes. For this reason, REST was initially proposed to silence the transcription of neuronal genes in non-neuronal cells. However, it has subsequently emerged as both a master regulator of neurogenesis and a factor with other essential roles in both neuronal and non-neuronal cells. Indeed, inappropriate REST expression can trigger apoptosis (Lawinger et al., 2000; Neumann et al., 2004).
A combination of bioinformatics and biochemical approaches has been used to identify binding sites and potential target genes of REST. Genome-wide chromatin immunoprecipitation studies have shown that REST can occupy several thousand RE1 motifs with the potential to regulate hundreds of different genes (Johnson et al., 2007; Otto et al., 2007). REST is therefore implicated in multiple biological processes and signalling pathways, for example regulating ion channels, growth factors or hormones, cytoskeletal proteins and other transcription factors (Bruce et al., 2004). Specific examples include regulation of MAD2 that impacts on mitosis and DNA recombination (Guardavaccaro et al., 2008), many neurosecretory proteins that affect presynaptic vesicle processing and exocytosis of secreted factors (Bruce et al., 2006; Pance et al., 2006; D'Alessandro et al., 2009), the deubiquitinating enzyme UCHL1 affecting ubiquitination and proteasome-mediated stability (Barrachina et al., 2007), and the VEGF receptor NRP1 that influences cell migration and angiogenesis (Kurschat et al., 2006). REST ablation impairs the production of laminin extracellular matrix components (Sun et al., 2008) and plays a role as a switch regulating potassium channel expression (Cheong et al., 2005). REST also interacts with several intracellular signal transduction cascades, including the PI3K (Westbrook et al., 2005), WNT (Nishihara et al., 2003) and Hedgehog (Gates et al., 2010) pathways. In addition to directly regulating mRNA transcription, REST also controls expression of a family of micro-RNAs that indirectly control other mRNA targets (Conaco et al., 2006), for example REST-mediated repression of micro-RNAs directs a switch of chromatin regulatory complexes essential for the transition to post-mitotic neurons (Yoo et al., 2009).
REST mediates its actions through interaction with a large repertoire of proteins that modify chromatin including the transcriptional repressor SIN3A/SIN3B at RD1, and the methylated CpG binding protein MeCP2 (Lunyak et al., 2002) along with many others at RD2. For example, the SMARCA4 (BRG1), SMARCC2 (BAF170) and SMARCE1 (BAF57) components of the SWI/SNF ATP-dependent chromatin-remodeling complex are recruited (Battaglioli et al., 2002). RCOR1 (coREST) is also recruited by REST to occupy RE1, and co-ordinates assembly of the BHC complex comprising the SWI/SNF component HMG20 (BRAF35), the scaffold PHF21A (BHC80), the histone deacetylases HDAC1/HDAC2 and the H3K4 demethylase KDM1A (LSD1) (Lee et al., 2005). Recruitment of the H3K9/H3K27 methyltransferase EHMT2 (G9a) (Roopra et al., 2004) appears to be dependent on MED12 (Ding et al., 2008) and CDYL (Mulligan et al., 2008). Together these complexes mediate transcriptional repression by remodeling chromatin so that histones become more tightly associated with DNA and less accessible to the transcriptional machinery (Ooi and Wood, 2007).
Homology REST is a member of the mammalian family of Krüppel-type zinc finger transcription factors. The closest paralog based on sequence homology to REST is ZNF407.

Mutations

Somatic Deletions of varying size encompassing the REST locus on chromosome 4 were detected in one-third of primary human colon tumors and colon cancer cell lines, suggesting that chromosomal deletions targeting REST are a frequent event in colon cancer (Westbrook et al., 2005). The REST locus has also been implicated in brain tumors, as an amplification site identified in human malignant glioma mapped to chromosome 4q12 (Schrock et al., 1994) and this region was lost in 30-80% of oligodendrogliomas or anaplastic oligodendrogliomas (Zhu et al., 1998). Another study of 161 patients diagnosed with nervous system tumors also screened samples for genetic alterations in REST (Blom et al., 2006). Although two non-synonymous SNPs were found in REST exon 3, which might affect the capacity of REST to bind target DNA, these were germ line changes and no cancer-associated truncating or activating mutations of REST were found. The same study reported low-level amplification of REST in both glioma and medulloblastoma, although high-level amplification was rare.

Implicated in

Entity Colon cancer
Note Deletions of the chromosome 4q12, region where REST is located, are frequent events in colon cancer.
Cytogenetics A single nucleotide deletion within REST exon 4 was identified in one cell line derived from colorectal adenocarcinoma. This results in a frameshift mutation and expression of REST-FS, a truncated variant with eight zinc fingers, but lacking the C-terminal repression domain RD2 (Westbrook et al., 2005).
  
Entity Small cell lung carcinoma (SCLC)
Note Altered REST function is associated with SCLC, because of reduced REST expression and an increased production of the REST splice variant sNRSF, that lacks part of the DNA-binding domain and the C-terminal repression domain RD2 (Coulson et al., 2000). This leads to inappropriate expression of genes like arginine vasopressin and the glycine receptor alpha in SCLC (Coulson et al., 1999; Neumann et al., 2004).
Prognosis For all types and stages of lung cancer diagnosed in the UK, the 1-year and 5-year survival is 28% and 8% respectively (Cancer Research UK CancerStats, 2006). SCG3 mRNA, a component of the REST-dependent neurosecretory transcriptional profile in lung cancer cells, was evaluated as a biomarker for noninvasive monitoring of neuroendocrine lung cancers and found to be associated with poor prognosis in limited disease SCLC patients (Moss et al., 2009).
  
Entity Non small cell lung carcinoma (NSCLC)
Note BRM/BRG1 are integral components of the SWI/SNF chromatin-remodeling complex, which forms part of a larger repression complex associated with REST. Loss of BRM/BRG1 is observed in some human NSCLC cell lines, and leads to de-repression of REST-restricted genes (Watanabe et al., 2006).
Prognosis Around 10% of NSCLC patients are reported to have BRM/BRG1 deficient lung carcinoma and this is associated with poor prognosis (Reisman et al., 2003; Fukuoka et al., 2004).
  
Entity Breast cancer
Note A tumor suppressor function for REST was identified through an RNAi library screen for genes that contributed to transformation in a breast cancer model associated with PI3K signaling (Westbrook et al., 2005). The TAC1 gene has been implicated in the development of breast and other cancers through production of peptides including substance P, which mediate resistance to apoptosis and radiation therapy. It was recently shown that, together with NFkB, REST represses TAC1 expression in mesenchymal stem cells. However, the level of REST decreases in breast cancer cells and inversely correlates with substance P production and an aggressive cellular phenotype (Reddy et al., 2009).
  
Entity Prostate cancer
Note Prostate tumors with a prominent neuroendocrine component are typically androgen independent and highly aggressive. In prostate adenocarcinoma cells, this acquisition of a neuroendocrine phenotype is associated with tumor progression and REST/NRSF levels decrease as the androgen resistance progresses. This directly induces IB1/JIP-1 transcription, which in turn modulates the JNK signaling pathway (Tawadros et al., 2005).
  
Entity Medulloblastoma
Note REST expression is generally low in adult brain permitting expression of RE1-restricted neuronal genes. However, REST is elevated in medulloblastoma cell lines and in 80% of human medulloblastoma tumors relatively to normal cerebellum sections, suggestive of an oncogenic role. Blocking endogenous REST function results in neuronal gene re-expression and apoptosis in both in vitro and in vivo medulloblastoma models (Lawinger et al., 2000; Fuller et al., 2005).
  
Entity Neuroblastoma
Note Alternative splice variants of REST were identified in murine and human neuroblastoma. It was suggested that changes in the structure or regulation of the REST gene may reflect or lead to the formation and progression of neuroblastoma tumors, and that the neuronal-specific exon/flanking introns may define a locus of somatic recombination (Palm et al., 1999).
  
Entity Huntington's disease
Note Wild type huntingtin protein (HTT) sequesters REST in the cytoplasm, inhibiting its function, whereas the mutant HTT protein cannot interact with REST resulting in higher levels of REST in the nucleus and repression of many target genes (Zuccato et al., 2007).
  
Entity Ischemia
Note Global ischemia triggers REST mRNA and protein expression. Knockdown of the REST gene rescues post-ischemic neurons from ischemia-induced cell death in an in vitro model (Calderone et al., 2003).
  
Entity Epilepsy
Note REST and the REST4 variant are differentially regulated in rodent hippocampal seizure models and correlate with expression of the proconvulsant substance P (Spencer et al., 2006). PRICKLE1 (REST/NRSF interacting LIM domain protein) normally binds to REST mediating its translocation to the cytoplasm, thereby preventing REST from silencing target genes. A PRICKLE1 mutation identified in individuals with progressive myoclonus epilepsy blocks the PRICKLE1 and REST interaction in vitro, resulting in constitutively active REST and inappropriate downregulation of REST target genes (Bassuk et al., 2008).
  

External links

Nomenclature
HGNC (Hugo)REST   9966
Cards
AtlasRESTID44266ch4q12
Entrez_Gene (NCBI)REST  5978  RE1-silencing transcription factor
GeneCards (Weizmann)REST
Ensembl (Hinxton)ENSG00000084093 [Gene_View]  chr4:57775079-57802010 [Contig_View]  REST [Vega]
ICGC DataPortalENSG00000084093
cBioPortalREST
AceView (NCBI)REST
Genatlas (Paris)REST
WikiGenes5978
SOURCE (Princeton)NM_001193508 NM_005612
Genomic and cartography
GoldenPath (UCSC)REST  -  4q12   chr4:57775079-57802010 +  4q12   [Description]    (hg19-Feb_2009)
EnsemblREST - 4q12 [CytoView]
Mapping of homologs : NCBIREST [Mapview]
OMIM600571   
Gene and transcription
Genbank (Entrez)AB209750 AF228045 BC017822 BC038985 BC132859
RefSeq transcript (Entrez)NM_001193508 NM_005612
RefSeq genomic (Entrez)AC_000136 NC_000004 NC_018915 NG_029447 NT_022853 NW_001838913 NW_004929319
Consensus coding sequences : CCDS (NCBI)REST
Cluster EST : UnigeneHs.307836 [ NCBI ]
CGAP (NCI)Hs.307836
Alternative Splicing : Fast-db (Paris)GSHG0022609
Alternative Splicing GalleryENSG00000084093
Gene ExpressionREST [ NCBI-GEO ]     REST [ SEEK ]   REST [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13127 (Uniprot)
NextProtQ13127  [Medical]
With graphics : InterProQ13127
Splice isoforms : SwissVarQ13127 (Swissvar)
Domaine pattern : Prosite (Expaxy)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (EBI)C2H2_Znf_fam [organisation]   REST [organisation]   Znf_C2H2 [organisation]   Znf_C2H2-like [organisation]   Znf_C2H2/integrase_DNA-bd [organisation]  
Related proteins : CluSTrQ13127
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Domain families : Smart (EMBL)ZnF_C2H2 (SM00355)  
DMDM Disease mutations5978
Blocks (Seattle)Q13127
PDB (SRS)2CZY   
PDB (PDBSum)2CZY   
PDB (IMB)2CZY   
PDB (RSDB)2CZY   
Human Protein AtlasENSG00000084093 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ13127
HPRD08990
IPIIPI00159969   IPI00816510   IPI00816294   IPI00816561   
Protein Interaction databases
DIP (DOE-UCLA)Q13127
IntAct (EBI)Q13127
FunCoupENSG00000084093
BioGRIDREST
InParanoidQ13127
Interologous Interaction database Q13127
IntegromeDBREST
STRING (EMBL)REST
Ontologies - Pathways
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  negative regulation of transcription from RNA polymerase II promoter  core promoter sequence-specific DNA binding  core promoter binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription  chromatin binding  sequence-specific DNA binding transcription factor activity  protein binding  nucleus  nucleus  cytosol  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  transcription factor binding  negative regulation of cell proliferation  negative regulation of gene expression  outward rectifier potassium channel activity  transcriptional repressor complex  negative regulation of aldosterone biosynthetic process  cellular response to drug  positive regulation of apoptotic process  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  negative regulation by host of viral transcription  transcription regulatory region DNA binding  negative regulation of neuron differentiation  negative regulation of transcription, DNA-templated  negative regulation of transcription, DNA-templated  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  negative regulation of calcium ion-dependent exocytosis  negative regulation of insulin secretion  metal ion binding  negative regulation of neurogenesis  cardiac muscle cell myoblast differentiation  histone H4 deacetylation  cellular response to electrical stimulus  cellular response to glucocorticoid stimulus  potassium ion transmembrane transport  negative regulation of cortisol biosynthetic process  negative regulation of dense core granule biogenesis  negative regulation of mesenchymal stem cell differentiation  negative regulation of amniotic stem cell differentiation  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  negative regulation of transcription from RNA polymerase II promoter  core promoter sequence-specific DNA binding  core promoter binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription  chromatin binding  sequence-specific DNA binding transcription factor activity  protein binding  nucleus  nucleus  cytosol  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  transcription factor binding  negative regulation of cell proliferation  negative regulation of gene expression  outward rectifier potassium channel activity  transcriptional repressor complex  negative regulation of aldosterone biosynthetic process  cellular response to drug  positive regulation of apoptotic process  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  negative regulation by host of viral transcription  transcription regulatory region DNA binding  negative regulation of neuron differentiation  negative regulation of transcription, DNA-templated  negative regulation of transcription, DNA-templated  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  negative regulation of calcium ion-dependent exocytosis  negative regulation of insulin secretion  metal ion binding  negative regulation of neurogenesis  cardiac muscle cell myoblast differentiation  histone H4 deacetylation  cellular response to electrical stimulus  cellular response to glucocorticoid stimulus  potassium ion transmembrane transport  negative regulation of cortisol biosynthetic process  negative regulation of dense core granule biogenesis  negative regulation of mesenchymal stem cell differentiation  negative regulation of amniotic stem cell differentiation  
Pathways : KEGGHuntington's disease   
Protein Interaction DatabaseREST
Wikipedia pathwaysREST
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)REST
snp3D : Map Gene to Disease5978
SNP (GeneSNP Utah)REST
SNP : HGBaseREST
Genetic variants : HAPMAPREST
Exome VariantREST
1000_GenomesREST 
ICGC programENSG00000084093 
Somatic Mutations in Cancer : COSMICREST 
CONAN: Copy Number AnalysisREST 
Mutations and Diseases : HGMDREST
Mutations and Diseases : intOGenREST
Genomic VariantsREST  REST [DGVbeta]
dbVarREST
ClinVarREST
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM600571   
MedgenREST
GENETestsREST
Disease Genetic AssociationREST
Huge Navigator REST [HugePedia]  REST [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneREST
Homology/Alignments : Family Browser (UCSC)REST
Phylogenetic Trees/Animal Genes : TreeFamREST
Chemical/Protein Interactions : CTD5978
Chemical/Pharm GKB GenePA34334
Clinical trialREST
Cancer Resource (Charite)ENSG00000084093
Other databases
Probes
Litterature
PubMed141 Pubmed reference(s) in Entrez
CoreMineREST
iHOPREST
OncoSearchREST

Bibliography

Comparative genomic hybridization of human malignant gliomas reveals multiple amplification sites and nonrandom chromosomal gains and losses.
Schrock E, Thiel G, Lozanova T, du Manoir S, Meffert MC, Jauch A, Speicher MR, Nurnberg P, Vogel S, Janisch W, et al.
Am J Pathol. 1994 Jun;144(6):1203-18.
PMID 8203461
 
REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons.
Chong JA, Tapia-Ramirez J, Kim S, Toledo-Aral JJ, Zheng Y, Boutros MC, Altshuller YM, Frohman MA, Kraner SD, Mandel G.
Cell. 1995 Mar 24;80(6):949-57.
PMID 7697725
 
The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes.
Schoenherr CJ, Anderson DJ.
Science. 1995 Mar 3;267(5202):1360-3.
PMID 7871435
 
A zinc finger protein that represses transcription of the human MHC class II gene, DPA.
Scholl T, Stevens MB, Mahanta S, Strominger JL.
J Immunol. 1996 Feb 15;156(4):1448-57.
PMID 8568247
 
NRSF/REST is required in vivo for repression of multiple neuronal target genes during embryogenesis.
Chen ZF, Paquette AJ, Anderson DJ.
Nat Genet. 1998 Oct;20(2):136-42.
PMID 9771705
 
Screening for loss of heterozygosity and microsatellite instability in oligodendrogliomas.
Zhu JJ, Santarius T, Wu X, Tsong J, Guha A, Wu JK, Hudson TJ, Black PM.
Genes Chromosomes Cancer. 1998 Mar;21(3):207-16.
PMID 9523195
 
Tumour-specific arginine vasopressin promoter activation in small-cell lung cancer.
Coulson JM, Stanley J, Woll PJ.
Br J Cancer. 1999 Aug;80(12):1935-44.
PMID 10471042
 
Neuron-specific splicing of zinc finger transcription factor REST/NRSF/XBR is frequent in neuroblastomas and conserved in human, mouse and rat.
Palm K, Metsis M, Timmusk T.
Brain Res Mol Brain Res. 1999 Sep 8;72(1):30-9.
PMID 10521596
 
A splice variant of the neuron-restrictive silencer factor repressor is expressed in small cell lung cancer: a potential role in derepression of neuroendocrine genes and a useful clinical marker.
Coulson JM, Edgson JL, Woll PJ, Quinn JP.
Cancer Res. 2000 Apr 1;60(7):1840-4.
PMID 10766169
 
The neuronal repressor REST/NRSF is an essential regulator in medulloblastoma cells.
Lawinger P, Venugopal R, Guo ZS, Immaneni A, Sengupta D, Lu W, Rastelli L, Marin Dias Carneiro A, Levin V, Fuller GN, Echelard Y, Majumder S.
Nat Med. 2000 Jul;6(7):826-31.
PMID 10888935
 
Role of zinc finger domains of the transcription factor neuron-restrictive silencer factor/repressor element-1 silencing transcription factor in DNA binding and nuclear localization.
Shimojo M, Lee JH, Hersh LB.
J Biol Chem. 2001 Apr 20;276(16):13121-6. Epub 2001 Jan 5.
PMID 11145971
 
REST repression of neuronal genes requires components of the hSWI.SNF complex.
Battaglioli E, Andres ME, Rose DW, Chenoweth JG, Rosenfeld MG, Anderson ME, Mandel G.
J Biol Chem. 2002 Oct 25;277(43):41038-45. Epub 2002 Aug 20.
PMID 12192000
 
Corepressor-dependent silencing of chromosomal regions encoding neuronal genes.
Lunyak VV, Burgess R, Prefontaine GG, Nelson C, Sze SH, Chenoweth J, Schwartz P, Pevzner PA, Glass C, Mandel G, Rosenfeld MG.
Science. 2002 Nov 29;298(5599):1747-52. Epub 2002 Oct 24.
PMID 12399542
 
Ischemic insults derepress the gene silencer REST in neurons destined to die.
Calderone A, Jover T, Noh KM, Tanaka H, Yokota H, Lin Y, Grooms SY, Regis R, Bennett MV, Zukin RS.
J Neurosci. 2003 Mar 15;23(6):2112-21.
PMID 12657670
 
The canonical Wnt pathway directly regulates NRSF/REST expression in chick spinal cord.
Nishihara S, Tsuda L, Ogura T.
Biochem Biophys Res Commun. 2003 Nov 7;311(1):55-63.
PMID 14575694
 
Loss of BRG1/BRM in human lung cancer cell lines and primary lung cancers: correlation with poor prognosis.
Reisman DN, Sciarrotta J, Wang W, Funkhouser WK, Weissman BE.
Cancer Res. 2003 Feb 1;63(3):560-6.
PMID 12566296
 
REST/NRSF-interacting LIM domain protein, a putative nuclear translocation receptor.
Shimojo M, Hersh LB.
Mol Cell Biol. 2003 Dec;23(24):9025-31.
PMID 14645515
 
Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes.
Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, Cataudella T, Leavitt BR, Hayden MR, Timmusk T, Rigamonti D, Cattaneo E.
Nat Genet. 2003 Sep;35(1):76-83. Epub 2003 Jul 27.
PMID 12881722
 
Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes.
Bruce AW, Donaldson IJ, Wood IC, Yerbury SA, Sadowski MI, Chapman M, Gottgens B, Buckley NJ.
Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10458-63. Epub 2004 Jul 6.
PMID 15240883
 
Chromatin remodeling factors and BRM/BRG1 expression as prognostic indicators in non-small cell lung cancer.
Fukuoka J, Fujii T, Shih JH, Dracheva T, Meerzaman D, Player A, Hong K, Settnek S, Gupta A, Buetow K, Hewitt S, Travis WD, Jen J.
Clin Cancer Res. 2004 Jul 1;10(13):4314-24.
PMID 15240517
 
Relaxation of glycine receptor and onconeural gene transcription control in NRSF deficient small cell lung cancer cell lines.
Neumann SB, Seitz R, Gorzella A, Heister A, Doeberitz MK, Becker CM.
Brain Res Mol Brain Res. 2004 Jan 5;120(2):173-81.
PMID 14741407
 
Localized domains of G9a-mediated histone methylation are required for silencing of neuronal genes.
Roopra A, Qazi R, Schoenike B, Daley TJ, Morrison JF.
Mol Cell. 2004 Jun 18;14(6):727-38.
PMID 15200951
 
Downregulated REST transcription factor is a switch enabling critical potassium channel expression and cell proliferation.
Cheong A, Bingham AJ, Li J, Kumar B, Sukumar P, Munsch C, Buckley NJ, Neylon CB, Porter KE, Beech DJ, Wood IC.
Mol Cell. 2005 Oct 7;20(1):45-52.
PMID 16209944
 
Transcriptional regulation: cancer, neurons and the REST.
Coulson JM.
Curr Biol. 2005 Sep 6;15(17):R665-8. (REVIEW)
PMID 16139198
 
Many human medulloblastoma tumors overexpress repressor element-1 silencing transcription (REST)/neuron-restrictive silencer factor, which can be functionally countered by REST-VP16.
Fuller GN, Su X, Price RE, Cohen ZR, Lang FF, Sawaya R, Majumder S.
Mol Cancer Ther. 2005 Mar;4(3):343-9.
PMID 15767543
 
An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation.
Lee MG, Wynder C, Cooch N, Shiekhattar R.
Nature. 2005 Sep 15;437(7057):432-5. Epub 2005 Aug 3.
PMID 16079794
 
IB1/JIP-1 controls JNK activation and increased during prostatic LNCaP cells neuroendocrine differentiation.
Tawadros T, Martin D, Abderrahmani A, Leisinger HJ, Waeber G, Haefliger JA.
Cell Signal. 2005 Aug;17(8):929-39. Epub 2005 Mar 3.
PMID 15894166
 
A genetic screen for candidate tumor suppressors identifies REST.
Westbrook TF, Martin ES, Schlabach MR, Leng Y, Liang AC, Feng B, Zhao JJ, Roberts TM, Mandel G, Hannon GJ, Depinho RA, Chin L, Elledge SJ.
Cell. 2005 Jun 17;121(6):837-48.
PMID 15960972
 
Molecular genetic analysis of the REST/NRSF gene in nervous system tumors.
Blom T, Tynninen O, Puputti M, Halonen M, Paetau A, Haapasalo H, Tanner M, Nupponen NN.
Acta Neuropathol. 2006 Oct;112(4):483-90. Epub 2006 Jul 6.
PMID 16823502
 
The transcriptional repressor REST is a critical regulator of the neurosecretory phenotype.
Bruce AW, Krejci A, Ooi L, Deuchars J, Wood IC, Dolezal V, Buckley NJ.
J Neurochem. 2006 Sep;98(6):1828-40.
PMID 16945103
 
Reciprocal actions of REST and a microRNA promote neuronal identity.
Conaco C, Otto S, Han JJ, Mandel G.
Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2422-7. Epub 2006 Feb 6.
PMID 16461918
 
Neuron restrictive silencer factor NRSF/REST is a transcriptional repressor of neuropilin-1 and diminishes the ability of semaphorin 3A to inhibit keratinocyte migration.
Kurschat P, Bielenberg D, Rossignol-Tallandier M, Stahl A, Klagsbrun M.
J Biol Chem. 2006 Feb 3;281(5):2721-9. Epub 2005 Dec 5.
PMID 16330548
 
A role for the transcriptional repressor REST in maintaining the phenotype of neurosecretory-deficient PC12 cells.
Pance A, Livesey FJ, Jackson AP.
J Neurochem. 2006 Dec;99(5):1435-44. Epub 2006 Oct 25.
PMID 17064356
 
Regulation and role of REST and REST4 variants in modulation of gene expression in in vivo and in vitro in epilepsy models.
Spencer EM, Chandler KE, Haddley K, Howard MR, Hughes D, Belyaev ND, Coulson JM, Stewart JP, Buckley NJ, Kipar A, Walker MC, Quinn JP.
Neurobiol Dis. 2006 Oct;24(1):41-52. Epub 2006 Jul 7.
PMID 16828291
 
SWI/SNF complex is essential for NRSF-mediated suppression of neuronal genes in human nonsmall cell lung carcinoma cell lines.
Watanabe H, Mizutani T, Haraguchi T, Yamamichi N, Minoguchi S, Yamamichi-Nishina M, Mori N, Kameda T, Sugiyama T, Iba H.
Oncogene. 2006 Jan 19;25(3):470-9.
PMID 16247481
 
Target genes of neuron-restrictive silencer factor are abnormally up-regulated in human myotilinopathy.
Barrachina M, Moreno J, Juves S, Moreno D, Olive M, Ferrer I.
Am J Pathol. 2007 Oct;171(4):1312-23. Epub 2007 Sep 6.
PMID 17823282
 
Genome-wide mapping of in vivo protein-DNA interactions.
Johnson DS, Mortazavi A, Myers RM, Wold B.
Science. 2007 Jun 8;316(5830):1497-502. Epub 2007 May 31.
PMID 17540862
 
Chromatin crosstalk in development and disease: lessons from REST.
Ooi L, Wood IC.
Nat Rev Genet. 2007 Jul;8(7):544-54. (REVIEW)
PMID 17572692
 
A new binding motif for the transcriptional repressor REST uncovers large gene networks devoted to neuronal functions.
Otto SJ, McCorkle SR, Hover J, Conaco C, Han JJ, Impey S, Yochum GS, Dunn JJ, Goodman RH, Mandel G.
J Neurosci. 2007 Jun 20;27(25):6729-39.
PMID 17581960
 
Widespread disruption of repressor element-1 silencing transcription factor/neuron-restrictive silencer factor occupancy at its target genes in Huntington's disease.
Zuccato C, Belyaev N, Conforti P, Ooi L, Tartari M, Papadimou E, MacDonald M, Fossale E, Zeitlin S, Buckley N, Cattaneo E.
J Neurosci. 2007 Jun 27;27(26):6972-83.
PMID 17596446
 
A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome.
Bassuk AG, Wallace RH, Buhr A, Buller AR, Afawi Z, Shimojo M, Miyata S, Chen S, Gonzalez-Alegre P, Griesbach HL, Wu S, Nashelsky M, Vladar EK, Antic D, Ferguson PJ, Cirak S, Voit T, Scott MP, Axelrod JD, Gurnett C, Daoud AS, Kivity S, Neufeld MY, Mazarib A, Straussberg R, Walid S, Korczyn AD, Slusarski DC, Berkovic SF, El-Shanti HI.
Am J Hum Genet. 2008 Nov;83(5):572-81. Epub 2008 Oct 30.
PMID 18976727
 
Mediator links epigenetic silencing of neuronal gene expression with x-linked mental retardation.
Ding N, Zhou H, Esteve PO, Chin HG, Kim S, Xu X, Joseph SM, Friez MJ, Schwartz CE, Pradhan S, Boyer TG.
Mol Cell. 2008 Aug 8;31(3):347-59.
PMID 18691967
 
Control of chromosome stability by the beta-TrCP-REST-Mad2 axis.
Guardavaccaro D, Frescas D, Dorrello NV, Peschiaroli A, Multani AS, Cardozo T, Lasorella A, Iavarone A, Chang S, Hernando E, Pagano M.
Nature. 2008 Mar 20;452(7185):365-9.
PMID 18354482
 
CDYL bridges REST and histone methyltransferases for gene repression and suppression of cellular transformation.
Mulligan P, Westbrook TF, Ottinger M, Pavlova N, Chang B, Macia E, Shi YJ, Barretina J, Liu J, Howley PM, Elledge SJ, Shi Y.
Mol Cell. 2008 Dec 5;32(5):718-26.
PMID 19061646
 
Huntingtin regulates RE1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) nuclear trafficking indirectly through a complex with REST/NRSF-interacting LIM domain protein (RILP) and dynactin p150 Glued.
Shimojo M.
J Biol Chem. 2008 Dec 12;283(50):34880-6. Epub 2008 Oct 15.
PMID 18922795
 
Rest-mediated regulation of extracellular matrix is crucial for neural development.
Sun YM, Cooper M, Finch S, Lin HH, Chen ZF, Williams BP, Buckley NJ.
PLoS One. 2008;3(11):e3656. Epub 2008 Nov 6.
PMID 18987749
 
Nontelomeric TRF2-REST interaction modulates neuronal gene silencing and fate of tumor and stem cells.
Zhang P, Pazin MJ, Schwartz CM, Becker KG, Wersto RP, Dilley CM, Mattson MP.
Curr Biol. 2008 Oct 14;18(19):1489-94. Epub 2008 Sep 25.
PMID 18818083
 
Expression of dense-core vesicles and of their exocytosis are governed by the repressive transcription factor NRSF/REST.
D'Alessandro R, Klajn A, Meldolesi J.
Ann N Y Acad Sci. 2009 Jan;1152:194-200. (REVIEW)
PMID 19161390
 
SCG3 transcript in peripheral blood is a prognostic biomarker for REST-deficient small cell lung cancer.
Moss AC, Jacobson GM, Walker LE, Blake NW, Marshall E, Coulson JM.
Clin Cancer Res. 2009 Jan 1;15(1):274-83.
PMID 19118055
 
RE-1-silencing transcription factor shows tumor-suppressor functions and negatively regulates the oncogenic TAC1 in breast cancer cells.
Reddy BY, Greco SJ, Patel PS, Trzaska KA, Rameshwar P.
Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4408-13. Epub 2009 Feb 25.
PMID 19246391
 
MicroRNA-mediated switching of chromatin-remodelling complexes in neural development.
Yoo AS, Staahl BT, Chen L, Crabtree GR.
Nature. 2009 Jul 30;460(7255):642-6. Epub 2009 Jun 28.
PMID 19561591
 
The transcriptional repressor REST/NRSF modulates hedgehog signaling.
Gates KP, Mentzer L, Karlstrom RO, Sirotkin HI.
Dev Biol. 2010 Apr 15;340(2):293-305. Epub 2010 Feb 1.
PMID 20122919
 
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Written05-2010Monica Faronato, Judy M Coulson
Physiology Department, School of Biomedical Sciences, Faculty of Health and Life Sciences, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK

Citation

This paper should be referenced as such :
Faronato, M ; Coulson, JM
REST (RE1-silencing transcription factor)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(2):-.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/RESTID44266ch4q12.html

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