“RE1-silencing transcription factor”的意思、由来-开放百科全书

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.^[1]^[2]^[3] REST is expressly involved in the repression of neural genes in non-neuronal cells.^[3]^[4] 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.^[5] 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.

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.^[1] REST is found to be down-regulated in elderly people with Alzheimer's disease.^[6]

REST contains 8 Cys₂His₂ zinc fingers and mediates gene repression by recruiting several chromatin-modifying enzymes.^[7]

REST expression strongly correlates with increased longevity. REST levels are highest in the brains of people who lived up to be 90 - 100s and remained cognitively intact. Levels stayed high specifically in the brain regions vulnerable to Alzheimer's, suggesting that they might be protected from dementia. It is assumed that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity.^[6] REST is also responsible for ischaemia induced neuronal cell death, in mouse models of brain ischaemia. Ischaemia, which results from reduced blood profusion 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.^[8] 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.^[9]

Interactions

References

1. ^¹{{cite web | title = Entrez Gene: REST RE1-silencing transcription factor| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5978| accessdate = }}
2. ^{{cite journal | vauthors = Schoenherr CJ, Anderson DJ | title = The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes | journal = Science | volume = 267 | issue = 5202 | pages = 1360–3 | date = March 1995 | pmid = 7871435 | doi = 10.1126/science.7871435 }}
3. ^¹{{cite journal | vauthors = Chong JA, Tapia-Ramírez J, Kim S, Toledo-Aral JJ, Zheng Y, Boutros MC, Altshuller YM, Frohman MA, Kraner SD, Mandel G | title = REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons | journal = Cell | volume = 80 | issue = 6 | pages = 949–57 | date = March 1995 | pmid = 7697725 | doi = 10.1016/0092-8674(95)90298-8 }}
4. ^{{cite journal | vauthors = Coulson JM | title = Transcriptional regulation: cancer, neurons and the REST | journal = Current Biology | volume = 15 | issue = 17 | pages = R665–8 | date = September 2005 | pmid = 16139198 | doi = 10.1016/j.cub.2005.08.032 }}
5. ^{{cite journal | vauthors = 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 | title = A genetic screen for candidate tumor suppressors identifies REST | journal = Cell | volume = 121 | issue = 6 | pages = 837–48 | date = June 2005 | pmid = 15960972 | doi = 10.1016/j.cell.2005.03.033 }}
6. ^¹{{cite journal | vauthors = Lu T, Aron L, Zullo J, Pan Y, Kim H, Chen Y, Yang TH, Kim HM, Drake D, Liu XS, Bennett DA, Colaiácovo MP, Yankner BA | title = REST and stress resistance in ageing and Alzheimer's disease | journal = Nature | volume = 507 | issue = 7493 | pages = 448–54 | date = March 2014 | pmid = 24670762 | doi = 10.1038/nature13163 | pmc=4110979}}
7. ^{{cite journal | vauthors = Ooi L, Wood IC | title = Chromatin crosstalk in development and disease: lessons from REST | journal = Nature Reviews Genetics | volume = 8 | issue = 7 | pages = 544–54 | date = July 2007 | pmid = 17572692 | doi = 10.1038/nrg2100 }}
8. ^{{cite journal | vauthors = Noh KM, Hwang JY, Follenzi A, Athanasiadou R, Miyawaki T, Greally JM, Bennett MV, Zukin RS | title = Repressor element-1 silencing transcription factor (REST)-dependent epigenetic remodeling is critical to ischemia-induced neuronal death | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 16 | pages = E962–71 | date = April 2012 | pmid = 22371606 | doi = 10.1073/pnas.1121568109 | pmc=3341013}}
9. ^{{cite journal | vauthors = Cavadas MA, Mesnieres M, Crifo B, Manresa MC, Selfridge AC, Keogh CE, Fabian Z, Scholz CC, Nolan KA, Rocha LM, Tambuwala MM, Brown S, Wdowicz A, Corbett D, Murphy KJ, Godson C, Cummins EP, Taylor CT, Cheong A | title = REST is a hypoxia-responsive transcriptional repressor | journal = Scientific Reports | volume = 6 | pages = 31355 | date = 17 Aug 2016 | pmid = 27531581 | doi = 10.1038/srep31355 | pmc=4987654}}
10. ^{{cite journal | vauthors = Andrés ME, Burger C, Peral-Rubio MJ, Battaglioli E, Anderson ME, Grimes J, Dallman J, Ballas N, Mandel G | title = CoREST: a functional corepressor required for regulation of neural-specific gene expression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 17 | pages = 9873–8 | date = August 1999 | pmid = 10449787 | pmc = 22303 | doi = 10.1073/pnas.96.17.9873 }}

Further reading

{{cite journal | vauthors = Ooi L, Wood IC | title = Chromatin crosstalk in development and disease: lessons from REST | journal = Nature Reviews Genetics | volume = 8 | issue = 7 | pages = 544–54 | date = July 2007 | pmid = 17572692 | doi = 10.1038/nrg2100 | lastauthoramp = yes }}

{{cite journal | vauthors = Chong JA, Tapia-Ramírez J, Kim S, Toledo-Aral JJ, Zheng Y, Boutros MC, Altshuller YM, Frohman MA, Kraner SD, Mandel G | title = REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons | journal = Cell | volume = 80 | issue = 6 | pages = 949–57 | date = March 1995 | pmid = 7697725 | doi = 10.1016/0092-8674(95)90298-8 }}

{{cite journal | vauthors = Schoenherr CJ, Anderson DJ | title = The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes | journal = Science | volume = 267 | issue = 5202 | pages = 1360–3 | date = March 1995 | pmid = 7871435 | doi = 10.1126/science.7871435 }}

{{cite journal | vauthors = Scholl T, Stevens MB, Mahanta S, Strominger JL | title = A zinc finger protein that represses transcription of the human MHC class II gene, DPA | journal = Journal of Immunology | volume = 156 | issue = 4 | pages = 1448–57 | date = February 1996 | pmid = 8568247 | doi = }}

{{cite journal | vauthors = Coulson JM | title = Transcriptional regulation: cancer, neurons and the REST | journal = Current Biology | volume = 15 | issue = 17 | pages = R665–8 | date = September 2005 | pmid = 16139198 | doi = 10.1016/j.cub.2005.08.032 }}

{{cite journal | vauthors = Thiel G, Lietz M, Cramer M | title = Biological activity and modular structure of RE-1-silencing transcription factor (REST), a repressor of neuronal genes | journal = The Journal of Biological Chemistry | volume = 273 | issue = 41 | pages = 26891–9 | date = October 1998 | pmid = 9756936 | doi = 10.1074/jbc.273.41.26891 }}

{{cite journal | vauthors = Andrés ME, Burger C, Peral-Rubio MJ, Battaglioli E, Anderson ME, Grimes J, Dallman J, Ballas N, Mandel G | title = CoREST: a functional corepressor required for regulation of neural-specific gene expression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 17 | pages = 9873–8 | date = August 1999 | pmid = 10449787 | pmc = 22303 | doi = 10.1073/pnas.96.17.9873 }}

{{cite journal | vauthors = Palm K, Metsis M, Timmusk T | title = Neuron-specific splicing of zinc finger transcription factor REST/NRSF/XBR is frequent in neuroblastomas and conserved in human, mouse and rat | journal = Brain Research. Molecular Brain Research | volume = 72 | issue = 1 | pages = 30–9 | date = September 1999 | pmid = 10521596 | doi = 10.1016/S0169-328X(99)00196-5 }}

{{cite journal | vauthors = Naruse Y, Aoki T, Kojima T, Mori N | title = Neural restrictive silencer factor recruits mSin3 and histone deacetylase complex to repress neuron-specific target genes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 24 | pages = 13691–6 | date = November 1999 | pmid = 10570134 | pmc = 24126 | doi = 10.1073/pnas.96.24.13691 }}

{{cite journal | vauthors = Grimes JA, Nielsen SJ, Battaglioli E, Miska EA, Speh JC, Berry DL, Atouf F, Holdener BC, Mandel G, Kouzarides T | title = The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex | journal = The Journal of Biological Chemistry | volume = 275 | issue = 13 | pages = 9461–7 | date = March 2000 | pmid = 10734093 | doi = 10.1074/jbc.275.13.9461 }}

{{cite journal | vauthors = Coulson JM, Edgson JL, Woll PJ, Quinn JP | title = 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 | journal = Cancer Research | volume = 60 | issue = 7 | pages = 1840–4 | date = April 2000 | pmid = 10766169 | doi = }}

{{cite journal | vauthors = Kojima T, Murai K, Naruse Y, Takahashi N, Mori N | title = Cell-type non-selective transcription of mouse and human genes encoding neural-restrictive silencer factor | journal = Brain Research. Molecular Brain Research | volume = 90 | issue = 2 | pages = 174–86 | date = June 2001 | pmid = 11406295 | doi = 10.1016/S0169-328X(01)00107-3 }}

{{cite journal | vauthors = Battaglioli E, Andrés ME, Rose DW, Chenoweth JG, Rosenfeld MG, Anderson ME, Mandel G | title = REST repression of neuronal genes requires components of the hSWI.SNF complex | journal = The Journal of Biological Chemistry | volume = 277 | issue = 43 | pages = 41038–45 | date = October 2002 | pmid = 12192000 | doi = 10.1074/jbc.M205691200 }}

{{cite journal | vauthors = Lunyak VV, Burgess R, Prefontaine GG, Nelson C, Sze SH, Chenoweth J, Schwartz P, Pevzner PA, Glass C, Mandel G, Rosenfeld MG | title = Corepressor-dependent silencing of chromosomal regions encoding neuronal genes | journal = Science | volume = 298 | issue = 5599 | pages = 1747–52 | date = November 2002 | pmid = 12399542 | doi = 10.1126/science.1076469 | citeseerx = 10.1.1.136.7131 }}

{{cite journal | vauthors = Lietz M, Hohl M, Thiel G | title = RE-1 silencing transcription factor (REST) regulates human synaptophysin gene transcription through an intronic sequence-specific DNA-binding site | journal = European Journal of Biochemistry / FEBS | volume = 270 | issue = 1 | pages = 2–9 | date = January 2003 | pmid = 12492469 | doi = 10.1046/j.1432-1033.2003.03360.x }}

{{cite journal | vauthors = Hersh LB, Shimojo M | title = Regulation of cholinergic gene expression by the neuron restrictive silencer factor/repressor element-1 silencing transcription factor | journal = Life Sciences | volume = 72 | issue = 18–19 | pages = 2021–8 | date = March 2003 | pmid = 12628452 | doi = 10.1016/S0024-3205(03)00065-1 }}

{{cite journal | vauthors = Kemp DM, Lin JC, Habener JF | title = Regulation of Pax4 paired homeodomain gene by neuron-restrictive silencer factor | journal = The Journal of Biological Chemistry | volume = 278 | issue = 37 | pages = 35057–62 | date = September 2003 | pmid = 12829700 | doi = 10.1074/jbc.M305891200 }}

{{cite journal | vauthors = Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, Cataudella T, Leavitt BR, Hayden MR, Timmusk T, Rigamonti D, Cattaneo E | title = Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes | journal = Nature Genetics | volume = 35 | issue = 1 | pages = 76–83 | date = September 2003 | pmid = 12881722 | doi = 10.1038/ng1219 }}

{{cite journal | vauthors = Martin D, Tawadros T, Meylan L, Abderrahmani A, Condorelli DF, Waeber G, Haefliger JA | title = Critical role of the transcriptional repressor neuron-restrictive silencer factor in the specific control of connexin36 in insulin-producing cell lines | journal = The Journal of Biological Chemistry | volume = 278 | issue = 52 | pages = 53082–9 | date = December 2003 | pmid = 14565956 | doi = 10.1074/jbc.M306861200 }}

{{cite journal | vauthors = Kuwahara K, Saito Y, Takano M, Arai Y, Yasuno S, Nakagawa Y, Takahashi N, Adachi Y, Takemura G, Horie M, Miyamoto Y, Morisaki T, Kuratomi S, Noma A, Fujiwara H, Yoshimasa Y, Kinoshita H, Kawakami R, Kishimoto I, Nakanishi M, Usami S, Saito Y, Harada M, Nakao K | title = NRSF regulates the fetal cardiac gene program and maintains normal cardiac structure and function | journal = The EMBO Journal | volume = 22 | issue = 23 | pages = 6310–21 | date = December 2003 | pmid = 14633990 | pmc = 291842 | doi = 10.1093/emboj/cdg601 }}

{{cite journal | vauthors = Kuwabara T, Hsieh J, Nakashima K, Taira K, Gage FH | title = A small modulatory dsRNA specifies the fate of adult neural stem cells | journal = Cell | volume = 116 | issue = 6 | pages = 779–93 | date = March 2004 | pmid = 15035981 | doi = 10.1016/S0092-8674(04)00248-X }}

Function

Interactions

References

Further reading

External links