NR1D1 (REV-ERBA) represses gene expression (Homo sapiens)

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2, 3, 5, 8672, 3, 5, 914nucleoplasmNR1D1 HDAC3 HDAC3 NCOR1 HDAC3 PPARGC1A gene ELOVL3 geneNCOR1NR1D1ferriheme b CLOCK geneHDAC3 NCOR1 NR1D1 NR1D1:heme:Corepressors:PPARGC1A geneARNTL genePPARGC1A geneNCOR1 NR1D1 ferriheme bNPAS2 geneferriheme b HDAC3 NR1D1 NR1D1:heme:Corepressors:CLOCK geneELOVL3 gene NR1D1:heme:Corepressors:NPAS2 geneNR1D1 ferriheme b ferriheme b ARNTL gene CLOCK gene NR1D1 gene NR1D1 geneNR1D1:heme:Corepressors:ELOVL3 geneNR1D1:heme:Corepressors:NR1D1 geneHDAC3NR1D1 NPAS2 gene NCOR1 ferriheme b NR1D1:heme:Corepressors:ARNTL geneferriheme b HDAC3 NCOR1 NCOR1 1


Description

REV-ERBA binds DNA elements very similar to those bound by the transcription activator RORA. RORAREV-ERBA bound to DNA and heme recruits the corepressors NCoR and HDAC3 to repress transcription. Thus REV-ERBA and RORA appear to compete to repress or activate genes, repectively. Source:Reactome.

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Bibliography

  1. Yin L, Wu N, Lazar MA.; ''Nuclear receptor Rev-erbalpha: a heme receptor that coordinates circadian rhythm and metabolism.''; PubMed Europe PMC Scholia
  2. Phelan CA, Gampe RT, Lambert MH, Parks DJ, Montana V, Bynum J, Broderick TM, Hu X, Williams SP, Nolte RT, Lazar MA.; ''Structure of Rev-erbalpha bound to N-CoR reveals a unique mechanism of nuclear receptor-co-repressor interaction.''; PubMed Europe PMC Scholia
  3. Raghuram S, Stayrook KR, Huang P, Rogers PM, Nosie AK, McClure DB, Burris LL, Khorasanizadeh S, Burris TP, Rastinejad F.; ''Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REV-ERBbeta.''; PubMed Europe PMC Scholia
  4. Yin L, Wu N, Curtin JC, Qatanani M, Szwergold NR, Reid RA, Waitt GM, Parks DJ, Pearce KH, Wisely GB, Lazar MA.; ''Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114863view16:37, 25 January 2021ReactomeTeamReactome version 75
113309view11:38, 2 November 2020ReactomeTeamReactome version 74
112520view15:48, 9 October 2020ReactomeTeamReactome version 73
101432view11:30, 1 November 2018ReactomeTeamreactome version 66
100970view21:08, 31 October 2018ReactomeTeamreactome version 65
100507view19:42, 31 October 2018ReactomeTeamreactome version 64
100053view16:25, 31 October 2018ReactomeTeamreactome version 63
99605view14:59, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93993view13:50, 16 August 2017ReactomeTeamreactome version 61
93601view11:28, 9 August 2017ReactomeTeamreactome version 61
88073view08:58, 26 July 2016RyanmillerOntology Term : 'regulatory pathway' added !
86708view09:24, 11 July 2016ReactomeTeamreactome version 56
83206view10:22, 18 November 2015ReactomeTeamVersion54
81587view13:07, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ARNTL gene ProteinENSG00000133794 (ENSEMBL)
ARNTL geneENSG00000133794 (ENSEMBL)
CLOCK gene ProteinENSG00000134852 (ENSEMBL)
CLOCK geneENSG00000134852 (ENSEMBL)
ELOVL3 gene ProteinENSG00000119915 (ENSEMBL)
ELOVL3 geneENSG00000119915 (ENSEMBL)
HDAC3 ProteinO15379 (Uniprot-TrEMBL)
HDAC3ProteinO15379 (Uniprot-TrEMBL)
NCOR1 ProteinO75376 (Uniprot-TrEMBL)
NCOR1ProteinO75376 (Uniprot-TrEMBL)
NPAS2 gene ProteinENSG00000170485 (ENSEMBL)
NPAS2 geneENSG00000170485 (ENSEMBL)
NR1D1 ProteinP20393 (Uniprot-TrEMBL)
NR1D1 gene ProteinENSG00000126368 (ENSEMBL)
NR1D1 geneENSG00000126368 (ENSEMBL)
NR1D1:heme:Corepressors:ARNTL geneComplexR-HSA-5663269 (Reactome)
NR1D1:heme:Corepressors:CLOCK geneComplexR-HSA-5663248 (Reactome)
NR1D1:heme:Corepressors:ELOVL3 geneComplexR-HSA-5663261 (Reactome)
NR1D1:heme:Corepressors:NPAS2 geneComplexR-HSA-5663274 (Reactome)
NR1D1:heme:Corepressors:NR1D1 geneComplexR-HSA-5663262 (Reactome)
NR1D1:heme:Corepressors:PPARGC1A geneComplexR-HSA-5663272 (Reactome)
NR1D1ProteinP20393 (Uniprot-TrEMBL)
PPARGC1A gene ProteinENSG00000109189 (ENSEMBL)
PPARGC1A geneENSG00000109189 (ENSEMBL)
ferriheme b MetaboliteCHEBI:36144 (ChEBI)
ferriheme bMetaboliteCHEBI:36144 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
ARNTL geneR-HSA-1368069 (Reactome)
CLOCK geneR-HSA-5663271 (Reactome)
ELOVL3 geneR-HSA-5663252 (Reactome)
HDAC3R-HSA-1368069 (Reactome)
HDAC3R-HSA-5663245 (Reactome)
HDAC3R-HSA-5663252 (Reactome)
HDAC3R-HSA-5663258 (Reactome)
HDAC3R-HSA-5663265 (Reactome)
HDAC3R-HSA-5663271 (Reactome)
NCOR1R-HSA-1368069 (Reactome)
NCOR1R-HSA-5663245 (Reactome)
NCOR1R-HSA-5663252 (Reactome)
NCOR1R-HSA-5663258 (Reactome)
NCOR1R-HSA-5663265 (Reactome)
NCOR1R-HSA-5663271 (Reactome)
NPAS2 geneR-HSA-5663245 (Reactome)
NR1D1 geneR-HSA-5663265 (Reactome)
NR1D1:heme:Corepressors:ARNTL geneArrowR-HSA-1368069 (Reactome)
NR1D1:heme:Corepressors:CLOCK geneArrowR-HSA-5663271 (Reactome)
NR1D1:heme:Corepressors:ELOVL3 geneArrowR-HSA-5663252 (Reactome)
NR1D1:heme:Corepressors:NPAS2 geneArrowR-HSA-5663245 (Reactome)
NR1D1:heme:Corepressors:NR1D1 geneArrowR-HSA-5663265 (Reactome)
NR1D1:heme:Corepressors:PPARGC1A geneArrowR-HSA-5663258 (Reactome)
NR1D1R-HSA-1368069 (Reactome)
NR1D1R-HSA-5663245 (Reactome)
NR1D1R-HSA-5663252 (Reactome)
NR1D1R-HSA-5663258 (Reactome)
NR1D1R-HSA-5663265 (Reactome)
NR1D1R-HSA-5663271 (Reactome)
PPARGC1A geneR-HSA-5663258 (Reactome)
R-HSA-1368069 (Reactome) NR1D1 (REV-ERBA) binds heme. The NR1D1:heme complex is then able to recruit the corepressors NCoR and HDAC3. Corepressors do not bind NR1D1 in the absence of heme. NR1D1:heme binds a RRE element in the promoter of the ARNTL (BMAL1) gene, recruits corepressors, and represses transcription.
R-HSA-5663245 (Reactome) NR1D1 (REV-ERBA) binds the promoter of the NPAS2 gene and recruits corepressors to repress transcription. Recruitment of repressors appears to depend on the binding of heme by NR1D1.
R-HSA-5663252 (Reactome) As inferred from mouse homologs, REV-ERBA (NR1D1) binds the promoter of the ELOVL3 gene and represses transcription, possibly by recruiting corepressors.
R-HSA-5663258 (Reactome) NR1D1 (REV-ERBA) binds heme and the promoter of the PGC-1alpha (PPARGC1A) gene. The REV-ERBA:heme complex recruits the corepressors NCoR and HDAC3 and represses transcription.
R-HSA-5663265 (Reactome) NR1D1 (REV-ERBA) binds its own promoter and represses its own expression.
R-HSA-5663271 (Reactome) NR1D1 (REV-ERBA) binds the promoter of the CLOCK gene and recruits corepressors to repress transcription. Recruitment of repressors appears to depend on the binding of heme by NR1D1.
ferriheme bR-HSA-1368069 (Reactome)
ferriheme bR-HSA-5663245 (Reactome)
ferriheme bR-HSA-5663252 (Reactome)
ferriheme bR-HSA-5663258 (Reactome)
ferriheme bR-HSA-5663265 (Reactome)
ferriheme bR-HSA-5663271 (Reactome)
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