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

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2, 6, 8, 9734, 6, 8, 915nucleoplasmHDAC3 CLOCK gene PPARGC1A gene PPARGC1A geneNR1D1:heme:Corepressors:ELOVL3 geneNR1D1 NR1D1:heme:Corepressors:ARNTL geneNCOR1 NR1D1 ELOVL3 gene NR1D1:heme:Corepressors:CLOCK geneHDAC3 ferriheme b NCOR1NR1D1 ELOVL3 geneHDAC3 NR1D1HDAC3NR1D1 NCOR1 NPAS2 gene HDAC3 ferriheme b ferriheme b HDAC3 NCOR1 NCOR1 ferriheme bferriheme b NR1D1:heme:Corepressors:NPAS2 geneferriheme b NR1D1 gene ferriheme b NR1D1 ARNTL gene HDAC3 ARNTL geneNR1D1:heme:Corepressors:NR1D1 geneNR1D1 geneNCOR1 NR1D1 NCOR1 CLOCK geneNPAS2 geneNR1D1:heme:Corepressors:PPARGC1A gene3


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. View original pathway at: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

View all...
NameTypeDatabase referenceComment
ARNTL gene ProteinENSG00000133794 (Ensembl)
ARNTL geneGeneProductENSG00000133794 (Ensembl)
CLOCK gene ProteinENSG00000134852 (Ensembl)
CLOCK geneGeneProductENSG00000134852 (Ensembl)
ELOVL3 gene ProteinENSG00000119915 (Ensembl)
ELOVL3 geneGeneProductENSG00000119915 (Ensembl)
HDAC3 ProteinO15379 (Uniprot-TrEMBL)
HDAC3ProteinO15379 (Uniprot-TrEMBL)
NCOR1 ProteinO75376 (Uniprot-TrEMBL)
NCOR1ProteinO75376 (Uniprot-TrEMBL)
NPAS2 gene ProteinENSG00000170485 (Ensembl)
NPAS2 geneGeneProductENSG00000170485 (Ensembl)
NR1D1 ProteinP20393 (Uniprot-TrEMBL)
NR1D1 gene ProteinENSG00000126368 (Ensembl)
NR1D1 geneGeneProductENSG00000126368 (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 geneGeneProductENSG00000109189 (Ensembl)
ferriheme b MetaboliteCHEBI:36144 (ChEBI)
ferriheme bMetaboliteCHEBI:36144 (ChEBI)

Annotated Interactions

View all...
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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