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RE1-silencing transcription factor (neural-restrictive silencer factor, X2 box repressor, REST, NRSF, XBR)
Function:
1) transcriptional repressor
2) binds neuron-restrictive silencer element (NRSE)
3) represses neuronal gene transcription in non-neuronal cells
4) restricts expression of neuronal genes by associating with 2 distinct corepressors, mSin3 & CoREST, which in turn recruit histone deacetylase to promoters of REST-regulated genes
5) mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating & demethylating specific sites on histones
6) transcriptional repression by REST-CDYL via recruitment of histone methyltransferase EHMT2 may be important in suppression of transformation
7) interacts with SIN3A, SIN3B & RCOR1
8) interacts with CDYL
9) interacts with EHMT1 & EHMT2 only in the presence of CDYL
10) part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 & EHMT2
Structure:
- contains 9 C2H2-type zinc fingers
Compartment:
- nucleus
Alternative splicing: named isoforms=4
Expression:
1) ubiquitous [1]
2) expressed at higher levels in lymphoid tissues including spleen, thymus, peripheral blood lymphocytes [1]
3) expressed in ovary [1]
4) expressed in non neuronal tissues & in undifferentiated neuronal progenitors, but not in differentiated neurons [2]
5) expression is low in prefrontal cortex of young individuals & increases with age [3]
Pathology:
- diminished expression of REST in prefrontal cortex of patients with mild cognitive impairment or Alzheimer's disease [3]
General
C2H2 type zinc finger protein
phosphoprotein
transcriptional silencer (transcriptional repressor)
Properties
SIZE: MW = 122 kD
entity length = 1097 aa
COMPARTMENT: cell nucleus
MOTIF: glycine-rich region {11-14}
binding site
SITE: 32-122
FOR-BINDING-OF: paired amphipathic helix protein sin3a
MOTIF: binding site
SITE: 43-57
FOR-BINDING-OF: paired amphipathic helix protein sin3b
Zn finger C2H2-type
SITE: 159-181
EFFECTOR-BOUND: Zn+2
Zn finger C2H2-type
SITE: 216-238
EFFECTOR-BOUND: Zn+2
Zn finger C2H2-type
SITE: 248-270
EFFECTOR-BOUND: Zn+2
Zn finger C2H2-type
SITE: 276-298
EFFECTOR-BOUND: Zn+2
Zn finger C2H2-type
SITE: 304-326
EFFECTOR-BOUND: Zn+2
Zn finger C2H2-type
SITE: 332-355
EFFECTOR-BOUND: Zn+2
Zn finger C2H2-type
SITE: 361-383
EFFECTOR-BOUND: Zn+2
Zn finger C2H2-type
SITE: 389-412
EFFECTOR-BOUND: Zn+2
lysine-rich region {400-603}
MOTIF: lysine residue (SEVERAL)
proline-rich region
SITE: 595-815
MOTIF: proline residue (SEVERAL)
Ser phosphorylation site {S864}
binding site
SITE: 1009-1087
FOR-BINDING-OF: REST corepressor 1
MOTIF: Zn finger C2H2-type
SITE: 1060-1082
EFFECTOR-BOUND: Zn+2
Database Correlations
OMIM 600571
UniProt Q13127
Entrez Gene 5978
Kegg hsa:5978
References
- UniProt :accession Q13127
- Schoenherr CJ & Anderson DJ
The neuron-restrictive silencer factor (NRSF): a coordinate
repressor of multiple neuron-specific genes.
Science 267:1360 1995
PMID: 7871435
- Lu T, Aron L, Zullo J et al
REST and stress resistance in ageing and Alzheimer's disease.
Nature. March 19, 2014
PMID: 24670762
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13163.html
- Tsai LH and Madabhushi R
Alzheimer's disease: A protective factor for the ageing brain.
Nature. March 19, 2014
PMID: 24670758
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13214.html
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/RESTID44266ch4q12.html