Affinage

RCOR1

REST corepressor 1 · UniProt Q9UKL0

Length
485 aa
Mass
53.3 kDa
Annotated
2026-06-10
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RCOR1 (CoREST) is the scaffolding subunit of the CoREST chromatin-modifying corepressor complex, assembling HDAC1/2 and the H3K4 demethylase LSD1 (KDM1A) into an integrated repressive machine (PMID:11171972, PMID:11102443). CoREST is essential for LSD1 activity on physiological nucleosomal substrates: recombinant LSD1 cannot demethylate H3K4 within nucleosomes, but CoREST stimulates and enables nucleosomal demethylation by enhancing LSD1-nucleosome engagement (PMID:16079794). Structural work explains this requirement—LSD1-CoREST forms an elongated bivalent clamp in which the CoREST SANT2 domain contacts nucleosomal and extranucleosomal DNA while the central CoREST linker forms a triple-helical bundle with the LSD1 Tower domain, positioning the catalytic domain to detach and oxidize the H3 tail (PMID:16885027, PMID:25730864, PMID:32396821, PMID:21142040). Within the assembled complex the LSD1 demethylase and HDAC1/2 deacetylase activities are conformationally and catalytically coupled (PMID:32101746). Beyond histone substrates, RCOR1 associates with RNA Polymerase II and deacetylates its CTD at lysine 7 to dampen productive elongation at active genes (PMID:35322029). RCOR1 lacks intrinsic sequence specificity and is instead recruited to chromatin by diverse transcription factors for context-specific repression, including REST, Gfi-1/1b, Nurr1, ZNF217, ZNF516, ZNF750 and INSM1 (PMID:10734093, PMID:17707228, PMID:19345186, PMID:25228645, PMID:28947780, PMID:28049845, PMID:22560925). Its activity is tuned post-translationally by SUMOylation (PIASxbeta/PIASγ as ligases, SENP1 as eraser) (PMID:18854179, PMID:29555846) and by CRL3-KBTBD4-mediated ubiquitin-dependent degradation, a process hijacked by cancer-associated KBTBD4 indels and by the molecular glue UM171 (PMID:35379950, PMID:39939761). Physiologically, Rcor1 is required for definitive erythropoiesis and restrains myeloid lineage drift—its loss arrests erythroid maturation and derepresses Csf2rb and HSC/progenitor genes (PMID:24652990, PMID:26119982)—and it sustains Foxp3+ Treg suppressive function (PMID:31917688). The complex also governs neural progenitor-to-neuron transitions and cortical neuron migration, in part downstream of Notch signaling (PMID:21878487, PMID:28049845, PMID:27112428).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2000 High

    Establishing that CoREST is a stable subunit of a defined HDAC complex answered whether it was a corepressor scaffold rather than a transient cofactor.

    Evidence Native complex purification and mass spectrometry resolving a ~9.5S CoREST-HDAC1/2 complex containing a FAD-dependent oxidoreductase (LSD1)

    PMID:11102443 PMID:11171972

    Open questions at the time
    • Catalytic role of the FAD oxidoreductase subunit not yet defined
    • Mechanism of SANT-domain-mediated assembly unresolved
  2. 2000 High

    Mapping CoREST's recruitment by REST clarified how a sequence-independent corepressor is targeted to specific loci.

    Evidence Co-IP and yeast two-hybrid showing CoREST binds the REST C-terminal repressor domain, distinct from mSin3A's N-terminal engagement

    PMID:10734093

    Open questions at the time
    • Did not establish genome-wide target repertoire
    • Relative contributions of Sin3 versus CoREST arms unresolved
  3. 2005 High

    Demonstrating that CoREST is obligatory for LSD1 demethylation of nucleosomes defined the functional reason the two co-assemble.

    Evidence In vitro reconstitution with recombinant subunits and nucleosomal demethylase assays, plus RNAi de-repression of REST target genes

    PMID:16079794

    Open questions at the time
    • Structural basis of CoREST-enhanced nucleosome engagement not yet shown
    • HDAC contribution to the same substrates not addressed
  4. 2007 High

    A series of crystal structures established the molecular architecture coupling CoREST DNA binding to LSD1 substrate recognition.

    Evidence X-ray structures of LSD1-CoREST alone, with H3 peptide, and with SNAIL1, plus SANT2 mutagenesis and demethylase assays

    PMID:16885027 PMID:17537733 PMID:21300290

    Open questions at the time
    • Structures used peptides/truncations rather than intact nucleosomes
    • How transcription-factor competition is regulated in vivo unclear
  5. 2010 High

    Thermodynamic and genetic analyses defined the LSD1-CoREST interface and a reciprocal stability dependence.

    Evidence ITC mapping the CoREST linker-LSD1 Tower interaction (Kd ~16 nM) and conditional LSD1 knockout in ES cells showing CoREST protein loss

    PMID:20713442 PMID:21142040

    Open questions at the time
    • Degradation pathway controlling CoREST stability when LSD1 is absent not identified
    • H3K56ac increase mechanism not linked to specific complex subunit
  6. 2015 High

    Solution and crosslinking studies resolved how CoREST presents the nucleosome, refining the catalytic mechanism.

    Evidence SAXS, semisynthetic nucleosome crosslinking, EMSA and photocrosslinking defining a 1:1 bivalent 'ergonomic clamp' aided by extranucleosomal DNA

    PMID:25730864 PMID:25916846

    Open questions at the time
    • Did not resolve high-resolution atomic contacts with the nucleosome
    • Dynamics during catalytic turnover not directly observed
  7. 2020 High

    A nucleosome-bound crystal structure and EM of the ternary complex revealed catalytic coupling and corrected prior engagement models.

    Evidence X-ray structure of LSD1/CoREST on a 191-bp nucleosome and EM of the LSD1-HDAC1-RCOR1 ternary complex with coupled enzymatic assays

    PMID:32101746 PMID:32396821

    Open questions at the time
    • Functional consequence of demethylase-deacetylase coupling in vivo not fully mapped
    • Catalytic activity of the commonly used LSD1(K661A) mutant complicates prior in vivo interpretations
  8. 2022 High

    Identification of a non-histone substrate extended RCOR1 function beyond chromatin marks.

    Evidence Genome-wide ChIP-seq, Co-IP and biochemical CTD deacetylation assays showing RCOR1 deacetylates RNA Pol II CTD K7 at active genes

    PMID:35322029

    Open questions at the time
    • The deacetylase responsible (RCOR1-associated HDAC versus RCOR1 directly) not definitively assigned
    • Genome-wide impact on elongation kinetics not quantified
  9. 2014 High

    Paralog and isoform comparisons explained how distinct RCOR family members tune complex output.

    Evidence Co-IP, SANT-domain mutagenesis, demethylase assays and domain chimeras showing CoREST1/2/3 differ in HDAC1/2 binding and LSD1 stimulation

    PMID:24820421 PMID:24843136

    Open questions at the time
    • In vivo division of labor among paralogs incompletely defined
    • How cells select specific RCOR paralogs at given loci unknown
  10. 2014 High

    Conditional knockouts established RCOR1's essential, lineage-specific roles in hematopoiesis and immunity.

    Evidence Mouse conditional Rcor1 knockouts with transplantation, colony assays, ChIP and tumor models in erythroid cells and Foxp3+ Tregs

    PMID:24652990 PMID:26119982 PMID:31917688

    Open questions at the time
    • Direct target gene networks beyond Csf2rb only partly defined
    • Whether erythroid and Treg phenotypes share common molecular targets unknown
  11. 2022 High

    Discovery of regulated CoREST degradation revealed a druggable axis and disease mechanism.

    Evidence Proteomics, ubiquitylation assays and cryo-EM showing CRL3-KBTBD4 (via cancer indels and UM171/IP6 molecular glues) recruits and degrades the CoREST complex

    PMID:35379950 PMID:39939761

    Open questions at the time
    • Endogenous physiological trigger for KBTBD4-mediated CoREST turnover not established
    • Downstream transcriptional consequences of degradation only partially mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RCOR1 switches between canonical repression and demethylase-independent gene-activating modes (e.g. AP-1/SWI-SNF in endocrine resistance) at a mechanistic level remains unresolved.
  • Molecular determinants selecting repressive versus activating CoREST recruitment unknown
  • Integration of SUMOylation, degradation and paralog usage in directing context-specific output not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0042393 histone binding 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2
Partners
FOXP3GFI1BHDAC1HDAC2INSM1KDM1ARESTZNF217
Complex memberships
CoREST complex (RCOR1-LSD1/KDM1A-HDAC1/2)REST corepressor complex

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CoREST is an integral component of a distinct HDAC complex (CoREST-HDAC) composed of HDAC1/2, CoREST, and a polyamine oxidase homolog; the HDAC1/2-interacting region of CoREST maps to a 179-aa region containing a SANT domain, and this region is required for CoREST corepressor function. ZNF217 (not REST) was found associated with this complex. Biochemical purification, Co-IP, domain mapping by truncation, functional repression assays Proceedings of the National Academy of Sciences of the United States of America High 11171972
2000 CoREST/KIAA0071 stably associates with HDAC1 and HDAC2 in a distinct ~9.5S complex (complex cI) that also contains a FAD-dependent oxidoreductase (KIAA0601/LSD1); the SANT domain of CoREST is shared with other HDAC1/2-interacting proteins and may mediate complex assembly. Native complex purification, mass spectrometry, glycerol gradient sedimentation The Journal of biological chemistry High 11102443
2000 mSin3A interacts with REST through REST's N-terminal repressor domain (via the PAH2 domain of mSin3A), and CoREST interacts with REST's C-terminal repressor domain; both corepressors associate with REST in mammalian cells, with mSin3A required constitutively and CoREST recruited for more specialized repressor functions. Co-IP in mammalian cells, yeast two-hybrid, yeast genetic rescue (Sin3-null rescue), in vivo repression assays The Journal of biological chemistry High 10734093
2005 CoREST is essential for LSD1 (BHC110)-mediated demethylation of H3K4 on nucleosomal substrates: recombinant LSD1 alone cannot demethylate nucleosomes, but LSD1-containing complexes can; in vitro reconstitution with recombinant subunits shows CoREST both stimulates demethylation on core histones and enables nucleosomal demethylation by enhancing LSD1-nucleosome association. Depletion of CoREST in cells leads to de-repression of REST-responsive genes and increased H3K4 methylation. In vitro reconstitution with recombinant subunits, histone demethylase assay on nucleosomal substrates, CoREST depletion (RNAi) with gene expression and histone modification readouts Nature High 16079794
2006 Crystal structure of the LSD1-CoREST complex reveals an elongated structure with a long stalk connecting the LSD1 catalytic domain and the CoREST SANT2 domain; CoREST SANT2 interacts with DNA, and disruption of the SANT2-DNA interaction diminishes CoREST-dependent nucleosomal demethylation by LSD1; the overall shape suggests bivalent nucleosome binding. X-ray crystallography, mutagenesis of CoREST SANT2 domain, nucleosomal demethylase activity assay Molecular cell High 16885027
2007 Crystal structure of the LSD1-CoREST complex bound to a substrate-like H3 peptide inhibitor reveals that CoREST plays an active role in substrate recognition; LSD1 recognizes a large segment of the H3 tail through a deep, negatively charged active-site pocket; the geometry is consistent with flavin-mediated oxidation of the substrate amino-methyl group. X-ray crystallography of LSD1-CoREST-peptide ternary complex The Journal of biological chemistry High 17537733
2007 CoREST and LSD1 mediate transcriptional repression by Gfi-1 and Gfi-1b in hematopoiesis: CoREST and LSD1 associate with Gfi-1/1b via the SNAG repression domain; Gfi-1b recruits these cofactors to target gene promoters in vivo; inhibition of CoREST and LSD1 perturbs erythroid, megakaryocytic, and granulocytic differentiation. Affinity purification/MS of Gfi-1b complexes, Co-IP, ChIP at target promoters, RNAi knockdown with differentiation assays Molecular cell High 17707228
2008 CoREST interacts with Hsp70 and represses HSF1-dependent transcription of the hsp70 gene; CoREST is bound to the hsp70 promoter under basal conditions and its binding increases during heat shock; knockdown of CoREST prevents Hsp70-mediated repression of HSF1-dependent transcription. Co-IP (CoREST-Hsp70), ChIP at hsp70 promoter, shRNA knockdown, reporter assays Molecular cell High 18657505
2008 ZNF198 binds preferentially to the intact LSD1-CoREST-HDAC1 (LCH) ternary complex but not individual subunits; ZNF198 and REST binding to LCH are mutually exclusive; ZNF198 stabilizes LCH on chromatin independently of LCH; SUMO modification of HDAC1 weakens its interaction with CoREST but stimulates its binding to ZNF198; the LCH- and HDAC1-SUMO-binding domains of ZNF198 map to MYM-type zinc finger repeats. Co-IP, GST pulldown, ChIP, domain mapping, in vitro SUMOylation assay, RNAi knockdown PloS one High 18806873
2008 CoREST is SUMOylated at lysine 294 by the E3 ligase PIASxbeta; SENP1 mediates desumoylation; mutation of the CoREST sumoylation site compromises its corepressor activity, indicating SUMO-1 modification is required for full repressive function. In vivo and in vitro sumoylation assays, Co-IP, mutagenesis of sumoylation site, reporter-based repression assays Biochemical and biophysical research communications Medium 18854179
2009 Nurr1 recruits the CoREST corepressor complex to NF-κB-p65 on inflammatory gene promoters in microglia and astrocytes in a signal-dependent manner, resulting in clearance of NF-κB-p65 and transcriptional repression of pro-inflammatory genes. Co-IP (Nurr1-CoREST), ChIP at inflammatory gene promoters, Nurr1 knockdown/overexpression with cytokine/gene expression readouts Cell High 19345186
2005 During HSV-1 infection, ICP0 interacts with CoREST and displaces HDAC1 from the CoREST/REST complex; subsequently, CoREST and HDAC1 are phosphorylated by viral protein kinases and partially translocated to the cytoplasm; these events enable derepression of viral gene expression. Co-IP of endogenous CoREST/REST/HDAC1 complex, immunofluorescence localization, infection with ICP0-mutant viruses Proceedings of the National Academy of Sciences of the United States of America High 15897453
2007 ICP0 blocks silencing of HSV DNA by displacing HDAC1 from the CoREST-REST complex; a truncated CoREST (CoREST 146-482) that displaces HDAC1 from the complex can functionally substitute for ICP0 to rescue viral replication in multiple cell lines. Recombinant virus construction, viral yield assays, Co-IP of CoREST/REST/HDAC1 complex Proceedings of the National Academy of Sciences of the United States of America High 17939992
2009 LSD1 is a key component of the CoREST/REST repressor complex engaged by HSV-1; in infected cells LSD1 is partially degraded or remains stably associated with CoREST and is partially translocated to the cytoplasm; LSD1 demethylates histones bound to viral α gene promoters to enable their expression. Co-IP, immunofluorescence, infection with ICP0-mutant and wild-type viruses, fractionation Journal of virology Medium 19193804
2010 Deletion of LSD1 in mouse ES cells causes a reduction in CoREST protein levels and associated HDAC activity, demonstrating that LSD1 is required for CoREST stability; this results in a global increase in H3K56 acetylation but not H3K4 methylation in ES cells. Conditional gene knockout in ES cells, Western blot for CoREST protein, HDAC activity assay, histone modification analysis Molecular and cellular biology High 20713442
2011 Crystal structure of LSD1-CoREST bound to a SNAIL1 peptide reveals molecular mimicry: the N-terminal residues of SNAIL1 bind to the enzyme active-site cleft mimicking the H3 tail, providing a mechanism by which transcription factors can competitively inhibit LSD1 substrate binding. X-ray crystallography of LSD1-CoREST-SNAIL1 peptide complex, molecular dynamics simulation Structure (London, England : 1993) High 21300290
2012 Sumoylation of Braf35 (a subunit of the LSD1-CoREST complex) is required for full repression of neuronal genes and for CoREST complex occupancy at target genes; Braf35-iBraf heterodimerization impairs Braf35 interaction with LSD1-CoREST and blocks Braf35 sumoylation, thereby antagonizing the complex's repressive activity. Sumoylation assays, Co-IP, ChIP, gain/loss-of-function in P19 cells and chick neural tube Proceedings of the National Academy of Sciences of the United States of America High 22570500
2011 CoREST depletion by in utero electroporation in mouse embryonic cortex markedly delays the transition of newborn cortical pyramidal neurons from multipolar to bipolar morphology and impairs onset of radial migration; this function requires LSD1 and is independent of REST. In utero electroporation (shRNA knockdown), live imaging/morphological analysis of cortical neuron migration Cerebral cortex High 21878487
2002 In C. elegans, spr-1 (CoREST ortholog) is a negative regulator of LIN-12/Notch signaling acting cell-autonomously in the nucleus; genetic epistasis places spr-1 upstream of Hindsight; human CoREST can substitute for SPR-1, demonstrating functional conservation. Genetic screen, suppressor analysis, genetic epistasis with lin-12 alleles, rescue with human CoREST, nuclear localization by imaging Genes & development High 12381669
2014 CoREST1 and CoREST2 differ in their interaction with HDAC1/2: a single non-conserved leucine in the first SANT domain of CoREST2 severely weakens its association with HDAC1/2, and CoREST2 represses transcription in an HDAC-independent manner; CoREST3 interacts equally with LSD1 but leads to reduced LSD1 catalytic efficiency and lower transcriptional repression; all three CoRESTs interact equally with LSD1. Biochemical purification, Co-IP, in vitro demethylase assay, domain mutagenesis, transcriptional repression reporter assays Molecular and cellular biology High 24820421
2014 Rcor3 competitively inhibits LSD1-mediated nucleosomal H3K4 demethylation, while Rcor1 and Rcor2 facilitate it; appending the SANT2 domain of Rcor1 to Rcor3 confers the ability to facilitate demethylation; Rcor3 is recruited to target genes by Gfi1b and LSD1, leading to inhibition of H3K4 demethylation and transcriptional derepression. In vitro nucleosomal demethylase assay, domain chimera construction, ChIP at endogenous targets, Co-IP, RNAi/overexpression in hematopoietic cells with differentiation readouts Proceedings of the National Academy of Sciences of the United States of America High 24843136
2014 Rcor1 conditional knockout in mice causes profound anemia due to arrest of definitive erythroid cells at the proerythroblast-to-basophilic erythroblast transition; Rcor1-null erythroid progenitors aberrantly form myeloid colonies; Csf2rb (CSF2 receptor β) is a direct target for both Rcor1 and Gfi1b in erythroid cells, and its derepression leads to CSF2-dependent phospho-Stat5 hypersensitivity. Conditional knockout mouse, colony assay, gene expression profiling, ChIP, cytokine signaling assays Blood High 24652990
2015 The corepressor Rcor1 is essential for murine erythropoiesis; conditional adult deletion causes complete cell-autonomous block in erythroid maturation; Rcor1-deficient monocytes show extensive cytokine-dependent self-renewal and overexpress HSC/progenitor genes including Gata2, Meis1, Hoxa9. Conditional knockout mouse (adult), bone marrow transplantation, lineage analysis, colony assays, gene expression Stem cells High 26119982
2014 ZNF750 interacts with RCOR1, KDM1A (LSD1), and CTBP1/2 through conserved PLNLS sequences; RCOR1 and KDM1A colocalize with ZNF750 at progenitor gene loci and are required for progenitor gene repression, while KLF4 (not KDM1A) is required for ZNF750-mediated activation of differentiation genes. Co-IP, ChIP-seq, gene depletion (RNAi) with gene expression readouts Genes & development High 25228645
2015 LSD1-CoREST functions as an 'ergonomic clamp' on nucleosomes, inducing detachment of the H3 tail from nucleosomal DNA to make it available for demethylation; CoREST's DNA-binding activity and LSD1's catalytic domain act cooperatively through a bivalent, competitive interaction with nucleosomal substrates. Covalent crosslinking of LSD1-CoREST to semisynthetic nucleosomal particles, SAXS, binding assays, site-directed mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 25730864
2015 Extranucleosomal DNA dramatically enhances LSD1/CoREST demethylase activity on nucleosome substrates; LSD1/CoREST binds the nucleosome as a 1:1 complex; both LSD1 and CoREST subunits make close contact with DNA around the nucleosome dyad and extranucleosomal DNA as shown by photocrosslinking. Demethylase activity assay with nucleosome variants, EMSA, photocrosslinking Nucleic acids research High 25916846
2017 PIASγ (SUMO E3 ligase) interacts with CoREST1 (RCOR1), CoREST2, and CoREST3, increases their protein stability, and facilitates their SUMOylation by SUMO-2; SUMO-conjugating enzyme Ubc9 facilitates SUMOylation without affecting protein levels; SUMOylation-deficient CoREST1 and CoREST3 maintain similar interactions with LSD1 and HDAC1/2 and similar repressor capacity. Co-IP, in vivo and in vitro SUMOylation assays, SENP-1 desumoylation, mutagenesis of acceptor lysines, repressor activity assays The Biochemical journal Medium 29555846
2017 ZNF516 physically associates with the CtBP/LSD1/CoREST complex and transcriptionally represses EGFR and other proliferation/motility genes; the ZNF516-CtBP/LSD1/CoREST complex inhibits proliferation and invasion of breast cancer cells. Co-IP, ChIP-seq, RNAi knockdown with proliferation/invasion assays, xenograft models Nature communications Medium 28947780
2017 RCOR1 forms complexes with REST corepressors RCOR2 and the transcription factor INSM1 in embryonic mouse brain progenitors; double knockout of Rcor1/2 causes excess neural progenitor production at the expense of neurons; Rest transcripts are upregulated in the double KO, and reducing Rest partially rescues the interganglionic sulcus closure defect. Co-IP (INSM1-RCOR1/2 complexes), conditional double knockout mouse, genetic epistasis (Rest rescue), gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 28049845
2020 The CoREST complex (RCOR1/2 scaffold, HDAC1/2, LSD1) exists in at least two distinct conformational states with different kinetics; the activities of LSD1 and HDAC1 within the complex are closely coupled, not independent; EM of the ternary complex reveals a bi-lobed structure with LSD1 and HDAC1 at opposite ends; EM of CoREST-nucleosome complex reveals a mode of chromatin engagement contrasting with previous models. Electron microscopy (EM) of ternary LSD1-HDAC1-RCOR1 complex and CoREST-nucleosome complex, enzymatic activity assays (demethylase and deacetylase cross-coupling) Cell reports High 32101746
2020 Crystal structure of LSD1/CoREST bound to a 191-bp nucleosome reveals that the LSD1 catalytic domain binds extranucleosomal DNA and is positioned ~100 Å from the nucleosome core; CoREST makes critical contacts with both histone and DNA components of the nucleosome, explaining its essential role in nucleosomal demethylation; the LSD1(K661A) mutant commonly used as catalytically inactive in vivo retains substantial H3K4 demethylase activity on nucleosomes. X-ray crystallography of LSD1/CoREST-nucleosome complex, demethylase activity assay with LSD1(K661A) mutant Molecular cell High 32396821
2020 RCOR1 is predominantly associated with transcriptionally active genes genome-wide; RCOR1 associates with RNA Polymerase II during transcription and deacetylates its CTD at lysine 7, dampening productive elongation at actively transcribing genes (non-canonical function independent of histone modification). ChIP-seq (genome-wide), Co-IP (RCOR1-POL II), biochemical deacetylation assay of POL II CTD Nature communications High 35322029
2020 Rcor1 (and Rcor2) is physically associated with Foxp3 in Tregs; conditional deletion of Rcor1 in Foxp3+ Tregs decreases peripheral Treg proportions, increases Treg expression of IL-2 and IFN-γ, impairs suppression of homeostatic proliferation, and enhances antitumor immunity. Co-IP (Rcor1-Foxp3), conditional knockout mouse, flow cytometry, allograft/tumor models The Journal of clinical investigation High 31917688
2022 CoREST is recruited to regulatory regions co-bound by ERα and FOXA1 in endocrine-sensitive breast cancer cells to regulate the estrogen pathway; during reprogramming towards endocrine resistance, CoREST is recruited to AP-1 sites, favors chromatin opening and cJUN binding, and promotes gene activation by controlling SWI/SNF recruitment independently of LSD1 demethylase activity. ChIP-seq, ATAC-seq, Co-IP, genetic/pharmacological CoREST inhibition, xenograft models Nature structural & molecular biology High 36344844
2017 Sumoylated histone H4 (suH4) stimulates LSD1 demethylase activity on nucleosomes through a mechanism dependent on the SUMO-interaction motif (SIM) in CoREST; the stimulatory effect of suH4 is spatially limited to the sumoylated nucleosome and does not extend to adjacent nucleosomes. Semisynthetic nucleosomes containing site-specifically sumoylated H4, in vitro demethylase activity assay, SIM mutation in CoREST ACS chemical biology High 28832116
2010 LSD1 and CoREST binding are thermodynamically characterized: the LSD1-CoREST(286-482) interaction has a Kd of ~16 nM (1:1 stoichiometry) driven by favorable enthalpy; the central binding determinant maps to the CoREST 'linker' region (residues 293-380), a central helix that interacts with the LSD1 coiled-coil Tower domain to form a triple-helical bundle. Isothermal titration calorimetry (ITC), CoREST truncation constructs Biochemistry High 21142040
2022 KBTBD4 cancer-associated indel mutations promote recruitment and ubiquitylation of CoREST (RCOR1) for proteasomal degradation; this neo-substrate recruitment drives epigenetic reprogramming, increases stemness, and alters transcriptional programs in medulloblastoma cells. Proteomics, ubiquitylation assays, Co-IP, gene expression analysis, KBTBD4 mutant vs wild-type comparison Cell death and differentiation High 35379950
2025 UM171 acts as a molecular glue to induce high-affinity interactions between KBTBD4 (CRL3 E3 ligase adaptor) and HDAC1/2 within the LSD1-CoREST complex, promoting asymmetric assembly and subsequent CoREST complex degradation; cryo-EM reveals a single UM171 molecule enables a pair of KELCH-repeat propeller domains to recruit the HDAC1 catalytic domain; inositol hexakisphosphate acts as a second molecular glue strengthening the interaction. Cryo-EM structure determination, proteomics, base editor scanning of KBTBD4 and HDAC1, chemical inhibitor studies Nature High 39939761
2019 AGS-associated mutations in RNase H2B impair its interaction with ZMYM3 and the CoREST complex (including RCOR1, HDAC2, KDM1A); ZMYM3 acts as a scaffold coordinating interactions between the CoREST deacetylase/demethylase complex and RNase H2. Co-IP/pulldown with AGS mutant vs wild-type RNase H2B, interaction mapping PloS one Medium 30889214
2023 GSE1 forms a complex with the HDAC1/CoREST co-repressor complex; loss of GSE1 impairs DNA damage response (ATR signaling, γH2AX formation); GSE1 is essential for binding of deubiquitinase USP22 to CoREST and for H2B K120 deubiquitination in response to DNA damage, but GSE1 loss does not affect CoREST histone deacetylation activity. AP-MS (affinity purification-mass spectrometry), phosphoproteomics, KO cell lines, H2B ubiquitination assay Nucleic acids research High 37878419
2007 NAC1 (a POZ/BTB protein) directly interacts with CoREST via its POZ/BTB domain; POZ/BTB homodimer formation is not required for the interaction; siRNA knockdown of NAC1 reverses CoREST-mediated transcriptional repression; endogenous interaction was confirmed in rat brain lysates. Co-IP in cell lines and rat brain, GST pulldown, domain mapping, siRNA knockdown with reporter assay Journal of neurochemistry Medium 17254023
2012 p120-catenin directly binds the REST-CoREST complex and negatively regulates it; p120-catenin displaces REST-CoREST from established gene targets, permitting their transcriptional activation; p120-catenin levels modulate Oct4, Nanog, and Sox2 and impact neural differentiation of mESCs. Co-IP/pulldown (p120-catenin and CoREST/REST), ChIP at target genes, p120-catenin overexpression/knockdown in mESCs with gene expression and differentiation readouts Journal of cell science Medium 25074806
2022 Nurr1 binds directly to the U3 region of the HIV LTR and recruits the CoREST/HDAC1/G9a/EZH2 transcription repressor complex to the HIV provirus, enhancing silencing; mutation of the Nurr1 DNA-binding domain blocks HIV transcription suppression; CoREST recruitment to the LTR was confirmed by ChIP. ChIP (Nurr1 and CoREST at HIV LTR), Nurr1 overexpression/knockdown, DNA-binding domain mutant, agonist treatment in iPSC-derived microglial cells PLoS pathogens High 35797416
2012 Gfi-1B p32 (a short isoform) recruits the LSD1-CoREST complex more efficiently than the major Gfi-1B p37 isoform; recruitment requires dimethylation of lysine 8 within the SNAG domain (via a KSKK motif); mutation of K8 prevents Gfi-1B p32-induced erythroid development. Co-IP, ChIP, selective knockdown of Gfi-1B p32 isoform, K8 mutagenesis, erythroid differentiation assays Journal of cell science High 22399799
2016 CoREST and LSD1 interact with RBPJ-κ in the Notch repressor complex in vitro; RBPJ-κ interaction is released upon Notch intracellular domain (NICD) overexpression; LSD1 binds the Hes1 promoter in vivo; knockdown of CoREST or LSD1 increases Hes1 expression and decreases Ngn2 in embryonic cortex; CoREST/LSD1 knockdown phenotypes (migration defect, increased Sox2/Tbr2 cells) are rescued by Notch loss-of-function. Co-IP (CoREST/LSD1 with RBPJ-κ), ChIP (LSD1 at Hes1 promoter), in utero electroporation knockdown, genetic epistasis with Notch Developmental neurobiology High 27112428
2012 The TGF-β-dependent active demethylation and expression of p15ink4b is blocked by the ZNF217/CoREST complex: ZNF217/CoREST/DNMT3A occupies the p15ink4b promoter; TGF-β treatment triggers loss of ZNF217/CoREST/DNMT3A and recruitment of SMAD2/3, CBP, and TDG; overexpression of ZNF217 prevents recruitment of SMAD2/3 and TDG and blocks active demethylation. ChIP and ChIP-seq at p15ink4b promoter, DNA immunoprecipitation (5mC and 5hmC), TGF-β stimulation, ZNF217 overexpression/knockdown Molecular cell High 22560925

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 775 19345186
2005 An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature 650 16079794
2008 The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience 558 19118166
2001 CoREST is an integral component of the CoREST- human histone deacetylase complex. Proceedings of the National Academy of Sciences of the United States of America 412 11171972
2007 Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1. Molecular cell 346 17707228
2006 Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase. Molecular cell 275 16885027
2000 Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1. The Journal of biological chemistry 275 11102443
2018 Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors. Nature communications 204 29302039
2007 Structural basis of LSD1-CoREST selectivity in histone H3 recognition. The Journal of biological chemistry 204 17537733
2000 The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex. The Journal of biological chemistry 202 10734093
2005 Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells. Proceedings of the National Academy of Sciences of the United States of America 166 15897453
2010 Lysine-specific demethylase 1 regulates the embryonic transcriptome and CoREST stability. Molecular and cellular biology 163 20713442
2007 Herpes simplex virus-infected cell protein 0 blocks the silencing of viral DNA by dissociating histone deacetylases from the CoREST-REST complex. Proceedings of the National Academy of Sciences of the United States of America 156 17939992
2014 ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes. Genes & development 121 25228645
2010 REST and CoREST are transcriptional and epigenetic regulators of seminal neural fate decisions. Cell cycle (Georgetown, Tex.) 119 21088488
2007 MeCP2 deficiency in the brain decreases BDNF levels by REST/CoREST-mediated repression and increases TRKB production. Epigenetics 118 18075316
2009 REST and CoREST modulate neuronal subtype specification, maturation and maintenance. PloS one 113 19997604
2020 Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex. Cell reports 108 32101746
2011 miR-124 acts through CoREST to control onset of Sema3A sensitivity in navigating retinal growth cones. Nature neuroscience 100 22138647
2020 Crystal Structure of the LSD1/CoREST Histone Demethylase Bound to Its Nucleosome Substrate. Molecular cell 95 32396821
2012 TGF-β-dependent active demethylation and expression of the p15ink4b tumor suppressor are impaired by the ZNF217/CoREST complex. Molecular cell 89 22560925
2011 Molecular mimicry and ligand recognition in binding and catalysis by the histone demethylase LSD1-CoREST complex. Structure (London, England : 1993) 85 21300290
2009 Differential deployment of REST and CoREST promotes glial subtype specification and oligodendrocyte lineage maturation. PloS one 81 19888342
2015 Interplay among nucleosomal DNA, histone tails, and corepressor CoREST underlies LSD1-mediated H3 demethylation. Proceedings of the National Academy of Sciences of the United States of America 76 25730864
2008 ZNF198 stabilizes the LSD1-CoREST-HDAC1 complex on chromatin through its MYM-type zinc fingers. PloS one 73 18806873
2008 The two functions of herpes simplex virus 1 ICP0, inhibition of silencing by the CoREST/REST/HDAC complex and degradation of PML, are executed in tandem. Journal of virology 73 18945770
2011 CoREST/LSD1 control the development of pyramidal cortical neurons. Cerebral cortex (New York, N.Y. : 1991) 71 21878487
2017 REST corepressors RCOR1 and RCOR2 and the repressor INSM1 regulate the proliferation-differentiation balance in the developing brain. Proceedings of the National Academy of Sciences of the United States of America 63 28049845
2013 Increased binding of stroke-induced long non-coding RNAs to the transcriptional corepressors Sin3A and coREST. ASN neuro 63 24063527
2012 LSD1/CoREST is an allosteric nanoscale clamp regulated by H3-histone-tail molecular recognition. Proceedings of the National Academy of Sciences of the United States of America 62 22802671
2012 Control of neuronal differentiation by sumoylation of BRAF35, a subunit of the LSD1-CoREST histone demethylase complex. Proceedings of the National Academy of Sciences of the United States of America 61 22570500
2014 MicroRNA targeting of CoREST controls polarization of migrating cortical neurons. Cell reports 59 24794437
2014 Differential properties of transcriptional complexes formed by the CoREST family. Molecular and cellular biology 59 24820421
2002 Suppressors of the egg-laying defective phenotype of sel-12 presenilin mutants implicate the CoREST corepressor complex in LIN-12/Notch signaling in C. elegans. Genes & development 57 12381669
2017 ZNF516 suppresses EGFR by targeting the CtBP/LSD1/CoREST complex to chromatin. Nature communications 55 28947780
2014 Antagonistic actions of Rcor proteins regulate LSD1 activity and cellular differentiation. Proceedings of the National Academy of Sciences of the United States of America 54 24843136
2013 Protein recognition by short peptide reversible inhibitors of the chromatin-modifying LSD1/CoREST lysine demethylase. ACS chemical biology 54 23721412
2010 Disruption of HDAC/CoREST/REST repressor by dnREST reduces genome silencing and increases virulence of herpes simplex virus. Proceedings of the National Academy of Sciences of the United States of America 54 20798038
2009 Engagement of the lysine-specific demethylase/HDAC1/CoREST/REST complex by herpes simplex virus 1. Journal of virology 53 19193804
2020 Inhibiting the coregulator CoREST impairs Foxp3+ Treg function and promotes antitumor immunity. The Journal of clinical investigation 52 31917688
2008 Genome analysis identifies the p15ink4b tumor suppressor as a direct target of the ZNF217/CoREST complex. Molecular and cellular biology 47 18625718
2004 A conserved role but different partners for the transcriptional corepressor CoREST in fly and mammalian nervous system formation. The Journal of neuroscience : the official journal of the Society for Neuroscience 43 15306652
2018 CoREST Complex-Selective Histone Deacetylase Inhibitors Show Prosynaptic Effects and an Improved Safety Profile To Enable Treatment of Synaptopathies. ACS chemical neuroscience 41 30496686
2020 More than a Corepressor: The Role of CoREST Proteins in Neurodevelopment. eNeuro 40 32075869
2008 CoREST represses the heat shock response mediated by HSF1. Molecular cell 40 18657505
2017 Chemically Sumoylated Histone H4 Stimulates Intranucleosomal Demethylation by the LSD1-CoREST Complex. ACS chemical biology 39 28832116
2015 Extranucleosomal DNA enhances the activity of the LSD1/CoREST histone demethylase complex. Nucleic acids research 39 25916846
2014 MicroRNA-432 contributes to dopamine cocktail and retinoic acid induced differentiation of human neuroblastoma cells by targeting NESTIN and RCOR1 genes. FEBS letters 39 24657437
2019 Epigenetic Regulator CoREST Controls Social Behavior in Ants. Molecular cell 38 31732456
2007 NAC1, a cocaine-regulated POZ/BTB protein interacts with CoREST. Journal of neurochemistry 37 17254023
2025 UM171 glues asymmetric CRL3-HDAC1/2 assembly to degrade CoREST corepressors. Nature 36 39939761
2010 The CoREST/REST repressor is both necessary and inimical for expression of herpes simplex virus genes. mBio 36 21221247
2014 p120-catenin regulates REST and CoREST, and modulates mouse embryonic stem cell differentiation. Journal of cell science 33 25074806
2012 A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain. Journal of cell science 32 22399799
2008 NF-Y substitutes H2A-H2B on active cell-cycle promoters: recruitment of CoREST-KDM1 and fine-tuning of H3 methylations. Nucleic acids research 30 18940868
2014 Corepressor Rcor1 is essential for murine erythropoiesis. Blood 28 24652990
2012 CoREST acts as a positive regulator of Notch signaling in the follicle cells of Drosophila melanogaster. Journal of cell science 28 22331351
2016 The chromatin modifying complex CoREST/LSD1 negatively regulates notch pathway during cerebral cortex development. Developmental neurobiology 27 27112428
2013 Differential transcriptional regulation of meis1 by Gfi1b and its co-factors LSD1 and CoREST. PloS one 26 23308270
2022 Disease-associated KBTBD4 mutations in medulloblastoma elicit neomorphic ubiquitylation activity to promote CoREST degradation. Cell death and differentiation 25 35379950
2022 Endocrine resistance and breast cancer plasticity are controlled by CoREST. Nature structural & molecular biology 25 36344844
2013 The role of the CoREST/REST repressor complex in herpes simplex virus 1 productive infection and in latency. Viruses 25 23628827
2013 Expanding the druggable space of the LSD1/CoREST epigenetic target: new potential binding regions for drug-like molecules, peptides, protein partners, and chromatin. PLoS computational biology 25 23874194
2022 Recruitment of the CoREST transcription repressor complexes by Nerve Growth factor IB-like receptor (Nurr1/NR4A2) mediates silencing of HIV in microglial cells. PLoS pathogens 24 35797416
2019 Targeting the GFI1/1B-CoREST Complex in Acute Myeloid Leukemia. Frontiers in oncology 22 31649884
2006 lin-35/Rb and the CoREST ortholog spr-1 coordinately regulate vulval morphogenesis and gonad development in C. elegans. Developmental biology 22 17070797
2022 Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin. Nature communications 20 35322029
2010 Thermodynamic characterization of the binding interaction between the histone demethylase LSD1/KDM1 and CoREST. Biochemistry 20 21142040
2012 LSD1/CoREST reversible opening-closing dynamics: discovery of a nanoscale clamp for chromatin and protein binding. Biochemistry 19 22468794
2001 Identification and localization of M-CoREST (1A13), a mouse homologue of the human transcriptional co-repressor CoREST, in the developing mouse CNS. Mechanisms of development 18 11578870
2021 HDAC2 targeting stabilizes the CoREST complex in renal tubular cells and protects against renal ischemia/reperfusion injury. Scientific reports 17 33907245
2018 Role of Epigenetic Regulation by the REST/CoREST/HDAC Corepressor Complex of Moderate NANOG Expression in Chicken Primordial Germ Cells. Stem cells and development 17 30032710
2013 Molecular dynamics simulations indicate an induced-fit mechanism for LSD1/CoREST-H3-histone molecular recognition. BMC biophysics 16 24274367
2015 The Corepressor Rcor1 Is Essential for Normal Myeloerythroid Lineage Differentiation. Stem cells (Dayton, Ohio) 15 26119982
2010 Depletion of CoREST does not improve the replication of ICP0 null mutant herpes simplex virus type 1. Journal of virology 14 20106915
2022 Activation of ABCC Genes by Cisplatin Depends on the CoREST Occurrence at Their Promoters in A549 and MDA-MB-231 Cell Lines. Cancers 13 35205642
2022 TBX2 acts as a potent transcriptional silencer of tumour suppressor genes through interaction with the CoREST complex to sustain the proliferation of breast cancers. Nucleic acids research 13 35687133
2020 MYT1 attenuates neuroblastoma cell differentiation by interacting with the LSD1/CoREST complex. Oncogene 13 32251364
2019 Distinct CoREST complexes act in a cell-type-specific manner. Nucleic acids research 13 31701127
2008 Sumoylation of CoREST modulates its function as a transcriptional repressor. Biochemical and biophysical research communications 13 18854179
2016 Expression profiling of RE1-silencing transcription factor (REST), REST corepressor 1 (RCOR1), and Synapsin 1 (SYN1) genes in human gliomas. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 11 27685921
2002 The Xiro-repressed gene CoREST is expressed in Xenopus neural territories. Mechanisms of development 11 11744385
2023 Inhibition of the CoREST Repressor Complex Promotes Wound Re-Epithelialization through the Regulation of Keratinocyte Migration. The Journal of investigative dermatology 9 37633457
2022 Efficacy of Vafidemstat in Experimental Autoimmune Encephalomyelitis Highlights the KDM1A/RCOR1/HDAC Epigenetic Axis in Multiple Sclerosis. Pharmaceutics 9 35890315
2019 Aicardi-Goutières Syndrome associated mutations of RNase H2B impair its interaction with ZMYM3 and the CoREST histone-modifying complex. PloS one 9 30889214
2011 Overexpression of either lysine-specific demethylase-1 or CLOCK, but not Co-Rest, improves long-term expression from a modified neurofilament promoter, in a helper virus-free HSV-1 vector system. Brain research 9 22208646
2023 GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage. Nucleic acids research 8 37878419
2020 RCOR1 directly binds to MED28 and weakens its inducing effect on cancer stem cell-like activity of oral cavity squamous cell carcinoma cells. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 8 32306431
2023 Gse1, a component of the CoREST complex, is required for placenta development in the mouse. Developmental biology 7 37019373
2023 CREB3 facilitates Donafenib resistance in hepatocellular carcinoma cells via the LSD1/CoREST/p65 axis by transcriptionally activating long noncoding RNA ZFAS1. Translational oncology 7 38641372
2012 Drosophila LSD1-CoREST demethylase complex regulates DPP/TGFβ signaling during wing development. Genesis (New York, N.Y. : 2000) 6 22965777
2025 CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond. Science advances 5 40479062
2010 REST corepressor (CoREST) repression induces phenotypic gene regulation in advanced osteoarthritic chondrocytes. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 5 20973059
2025 TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes STK11-Mutant Tumors to Anti-PD-1 Immunotherapy. Cancer research 4 40882030
2023 REST, RCOR1 and RCOR2 expression is reduced in osteoarthritic chondrocytes and contributes to increasing MMP13 and ADAMTS5 expression through upregulating HES1. Cellular signalling 4 37442513
2020 Pilocarpine-induced seizures associate with modifications of LSD1/CoREST/HDAC1/2 epigenetic complex and repressive chromatin in mice hippocampus. Biochemistry and biophysics reports 4 33426312
2018 PIASγ controls stability and facilitates SUMO-2 conjugation to CoREST family of transcriptional co-repressors. The Biochemical journal 4 29555846
2017 Exploring the Active Center of the LSD1/CoREST Complex by Molecular Dynamics Simulation Utilizing Its Co-crystallized Co-factor Tetrahydrofolate as a Probe. Journal of chemical information and modeling 4 29161028
2025 The Histone Demethylase LSD1/ZNF217/CoREST Complex is a Major Restriction Factor of Epstein-Barr Virus Lytic Reactivation. Research square 3 39877093
2021 Silencing CoREST inhibits the viability and migration of fibroblast-like synoviocytes in TNF-α-induced rheumatoid arthritis. Experimental and therapeutic medicine 3 35069829

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