RE1-silencing transcription factor

RE1-Silencing Transcription factor (REST), also known as Neuron-Restrictive Silencer Factor (NRSF), is a protein which in humans is encoded by the REST gene, and acts as a transcriptional repressor.^[5][6][7] REST is expressly involved in the repression of neural genes in non-neuronal cells.^[7][8] Many genetic disorders have been tied to alterations in the REST expression pattern, including colon and small-cell lung carcinomas found with truncated versions of REST.^[9] In addition to these cancers, defects in REST have also been attributed a role in Huntington Disease, neuroblastomas, and the effects of epileptic seizures and ischemia.

REST
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2CZY
Identifiers
Aliases	REST, Rest, 2610008J04Rik, AA407358, NRSF, XBR, REST4, WT6, RE1 silencing transcription factor, GINGF5, HGF5, DFNA27
External IDs	OMIM: 600571; MGI: 104897; HomoloGene: 4099; GeneCards: REST; OMA:REST - orthologs
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q12 Start 56,907,876 bp[1] End 56,966,808 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 C3.3 Start 77,413,338 bp[2] End 77,434,279 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gonad mucosa of paranasal sinus testicle Achilles tendon epithelium of nasopharynx epithelium of colon Epithelium of choroid plexus retinal pigment epithelium bone marrow cells oral cavity Top expressed in external carotid artery internal carotid artery zygote superior surface of tongue cumulus cell gallbladder human fetus secondary oocyte primary oocyte Gonadal ridge More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding outward rectifier potassium channel activity DNA-binding transcription activator activity, RNA polymerase II-specific transcription factor binding metal ion binding core promoter sequence-specific DNA binding protein binding nucleic acid binding DNA-binding transcription repressor activity, RNA polymerase II-specific histone deacetylase activity chromatin binding DNA-binding transcription factor activity DNA-binding transcription factor activity, RNA polymerase II-specific RNA polymerase II cis-regulatory region sequence-specific DNA binding RNA polymerase II core promoter sequence-specific DNA binding Cellular component cytosol nucleoplasm transcription repressor complex nucleus cytoplasm histone methyltransferase complex Biological process cellular response to electrical stimulus negative regulation of dense core granule biogenesis negative regulation of insulin secretion negative regulation of cortisol biosynthetic process negative regulation of transcription by RNA polymerase II transcription by RNA polymerase II negative regulation of gene expression transcription, DNA-templated negative regulation of amniotic stem cell differentiation positive regulation of transcription, DNA-templated negative regulation of mesenchymal stem cell differentiation histone H4 deacetylation positive regulation of cysteine-type endopeptidase activity involved in apoptotic process cellular response to glucocorticoid stimulus negative regulation of calcium ion-dependent exocytosis hematopoietic progenitor cell differentiation positive regulation of transcription by RNA polymerase II negative regulation of cell population proliferation negative regulation of aldosterone biosynthetic process negative regulation of transcription, DNA-templated cardiac muscle cell myoblast differentiation negative regulation of neurogenesis potassium ion transmembrane transport regulation of transcription, DNA-templated positive regulation of apoptotic process negative regulation of neuron differentiation regulation of transcription by RNA polymerase II regulation of alternative mRNA splicing, via spliceosome response to hypoxia regulation of gene expression positive regulation of neuron differentiation regulation of osteoblast differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5978 19712 Ensembl ENSG00000084093 ENSMUSG00000029249 UniProt Q13127 Q8VIG1 RefSeq (mRNA) NM_001193508 NM_005612 NM_001363453 NM_011263 RefSeq (protein) NP_001180437 NP_005603 NP_001350382 NP_035393 Location (UCSC) Chr 4: 56.91 – 56.97 Mb Chr 5: 77.41 – 77.43 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene encodes a transcriptional repressor which represses neuronal genes in non-neuronal tissues. It is a member of the Kruppel-type zinc finger transcription factor family. It represses transcription by binding a DNA sequence element called the neuron-restrictive silencer element (NRSE, also known as RE1). The protein is also found in undifferentiated neuronal progenitor cells, and it is thought that this repressor may act as a master negative regulator of neurogenesis. Alternatively spliced transcript variants have been described; however, their full length nature has not been determined.^[5] REST is found to be down-regulated in elderly people with Alzheimer's disease.^[10]

REST contains 8 Cys₂His₂ zinc fingers and mediates gene repression by recruiting several chromatin-modifying enzymes.^[11]

• 
  NRSF bound to DNA and cofactors on each of its two cofactor binding domains.
• 
  Chromatin remodeling occurs, causing the gene to be 'turned off'.

REST is also responsible for ischaemia induced neuronal cell death, in mouse models of brain ischaemia. Ischaemia, which results from reduced blood perfusion of tissues, decreasing nutrient and oxygen supply, induces REST transcription and nuclear accumulation, leading to the epigenetic repression of neuronal genes leading to cell death.^[12] The mechanism beyond REST induction in ischaemia, might be tightly linked to its oxygen-dependent nuclear translocation and repression of target genes in hypoxia (low oxygen) where REST fulfils the functions of a master regulator of gene repression in hypoxia.^[13]

Interactions

RE1-silencing transcription factor has been shown to interact with RCOR1.^[14]