RE1-silencing transcription factor (Neural-restrictive silencer factor) (X2 box repressor)
1_MATQV 6_ MGQSS 11_ GGGGL 16_ FTSSG 21_ NIGMA 26_ LPNDM 31_ YDLHD 36_ LSKAE 41_ LAAPQ 46_ LIMLA 51_ NVALT 56_ GEVNG 61_ SCCDY 66_ LVGEE 71_ RQMAE 76_ LMPVG 81_ DNNFS 86_ DSEEG 91_ EGLEE 96_ SADIK 101_ GEPHG 106_ LENME 111_ LRSLE 116_ LSVVE 121_ PQPVF 126_ EASGA 131_ PDIYS 136_ SNKDL 141_ PPETP 146_ GAEDK 151_ GKSSK 156_ TKPFR 161_ CKPCQ 166_ YEAES 171_ EEQFV 176_ HHIRV 181_ HSAKK 186_ FFVEE 191_ SAEKQ 196_ AKARE 201_ SGSST 206_ AEEGD 211_ FSKGP 216_ IRCDR 221_ CGYNT 226_ NRYDH 231_ YTAHL 236_ KHHTR 241_ AGDNE 246_ RVYKC 251_ IICTY 256_ TTVSE 261_ YHWRK 266_ HLRNH 271_ FPRKV 276_ YTCGK 281_ CNYFS 286_ DRKNN 291_ YVQHV 296_ RTHTG 301_ ERPYK 306_ CELCP 311_ YSSSQ 316_ KTHLT 321_ RHMRT 326_ HSGEK 331_ PFKCD 336_ QCSYV 341_ ASNQH 346_ EVTRH 351_ ARQVH 356_ NGPKP 361_ LNCPH 366_ CDYKT 371_ ADRSN 376_ FKKHV 381_ ELHVN 386_ PRQFN 391_ CPVCD 396_ YAASK 401_ KCNLQ 406_ YHFKS 411_ KHPTC 416_ PNKTM 421_ DVSKV 426_ KLKKT 431_ KKREA 436_ DLPDN 441_ ITNEK 446_ TEIEQ 451_ TKIKG 456_ DVAGK 461_ KNEKS 466_ VKAEK 471_ RDVSK 476_ EKKPS 481_ NNVSV 486_ IQVTT 491_ RTRKS 496_ VTEVK 501_ EMDVH 506_ TGSNS 511_ EKFSK 516_ TKKSK 521_ RKLEV 526_ DSHSL 531_ HGPVN 536_ DEESS 541_ TKKKK 546_ KVESK 551_ SKNNS 556_ QEVPK 561_ GDSKV 566_ EENKK 571_ QNTCM 576_ KKSTK 581_ KKTLK 586_ NKSSK 591_ KSSKP 596_ PQKEP 601_ VEKGS 606_ AQMDP 611_ PQMGP 616_ APTEA 621_ VQKGP 626_ VQVEP 631_ PPPME 636_ HAQME 641_ GAQIR 646_ PAPDE 651_ PVQME 656_ VVQEG 661_ PAQKE 666_ LLPPV 671_ EPAQM 676_ VGAQI 681_ VLAHM 686_ ELPPP 691_ METAQ 696_ TEVAQ 701_ MGPAP 706_ MEPAQ 711_ MEVAQ 716_ VESAP 721_ MQVVQ 726_ KEPVQ 731_ MELSP 736_ PMEVV 741_ QKEPV 746_ QIELS 751_ PPMEV 756_ VQKEP 761_ VKIEL 766_ SPPIE 771_ VVQKE 776_ PVQME 781_ LSPPM 786_ GVVQK 791_ EPAQR 796_ EPPPP 801_ REPPL 806_ HMEPI 811_ SKKPP 816_ LRKDK 821_ KEKSN 826_ MQSER 831_ ARKEQ 836_ VLIEV 841_ GLVPV 846_ KDSWL 851_ LKESV 856_ STEDL 861_ SPPSP 866_ PLPKE 871_ NLREE 876_ ASGDQ 881_ KLLNT 886_ GEGNK 891_ EAPLQ 896_ KVGAE 901_ EADES 906_ LPGLA 911_ ANINE 916_ STHIS 921_ SSGQN 926_ LNTPE 931_ GETLN 936_ GKHQT 941_ DSIVC 946_ EMKMD 951_ TDQNT 956_ RENLT 961_ GINST 966_ VEEPV 971_ SPMLP 976_ PSAVE 981_ EREAV 986_ SKTAL 991_ ASPPA 996_ TMAAN 1001_ ESQEI 1006_ DEDEG 1011_ IHSHE 1016_ GSDLS 1021_ DNMSE 1026_ GSDDS 1031_ GLHGA 1036_ RPVPQ 1041_ ESSRK 1046_ NAKEA 1051_ LAVKA 1056_ AKGDF 1061_ VCIFC 1066_ DRSFR 1071_ KGKDY 1076_ SKHLN 1081_ RHLVN 1086_ VYYLE 1091_EAAQG
1: Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells (PubMed:11741002, PubMed:11779185, PubMed:12399542, PubMed:26551668, PubMed:7697725, PubMed:7871435, PubMed:8568247). 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)
2: Binds to the 3' region of the neuron-restrictive silencer element (NRSE), with lower affinity than full-length REST isoform 1 (By similarity). Exhibits weaker repressor activity compared to isoform 1 (PubMed:11779185). May negatively regulate the repressor activity of isoform 1 by binding to isoform 1, thereby preventing its binding to NRSE and leading to derepression of target genes (PubMed:11779185). However, in another study, does not appear to be implicated in repressor activity of a NRSE motif-containing reporter construct nor in inhibitory activity on the isoform 1 transcriptional repressor activity (PubMed:11741002). Post-transcriptional inactivation of REST by SRRM4-dependent alternative splicing into isoform 3 is required in mechanosensory hair cells in the inner ear for derepression of neuronal genes and hearing (By similarity)