RE1-silencing transcription factor - Q13127 (REST_HUMAN)


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Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells (PubMed:12399542, PubMed:26551668, PubMed:7697725, PubMed:7871435, PubMed:8568247, PubMed:11741002, PubMed:11779185). 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 (PubMed:10449787, PubMed:10734093). 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 (By similarity). Transcriptional repression by REST-CDYL via the recruitment of histone methyltransferase EHMT2 may be important in transformation suppression (PubMed:19061646). 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 (By similarity). 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 (PubMed:11779185). 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 (By similarity). Thereby is involved in maintaining the quiescent state of adult neural stem cells and preventing premature differentiation into mature neurons (PubMed:21258371). 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 (By similarity). Acts as a regulator of osteoblast differentiation (By similarity). Key repressor of gene expression in hypoxia; represses genes in hypoxia by direct binding to an RE1/NRSE site on their promoter regions (PubMed:27531581). 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 (PubMed:24670762). 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 (By similarity). After ischemia, might play a role in repression of miR-132 expression in hippocampal neurons, thereby leading to neuronal cell death (By similarity). Negatively regulates the expression of SRRM3 in breast cancer cell lines (PubMed:26053433). UniProt
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Subunit Structure
Isoform 1 and isoform 3 form heterodimers (By similarity). Isoform 3: Forms homodimers and homooligomers; binds to the neuron-restrictive silencer element (NRSE) as monomer (By similarity). Interacts with SIN3A, SIN3B and RCOR1 (PubMed:10449787, PubMed:10734093, PubMed:16288918). Interacts with CDYL (PubMed:19061646). Interacts with EHMT1 and EHMT2 only in the presence of CDYL (PubMed:19061646). Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2 (PubMed:19061646). Interacts (via zinc-finger DNA-binding domain) with ZFP90 (via N- and C-termini); the interaction inhibits REST repressor activity (PubMed:21284946). Interacts (via C2H2-type zinc finger 5) with PRICKLE1 (PubMed:14645515, PubMed:16442230). Interacts with FBXW11 and BTRC (PubMed:18354482). Interacts with USP7 (PubMed:21258371). UniProt
The C2H2-type zinc finger 5 is required for nuclear localization. UniProt
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