Pathway
Expression of BMAL (ARNTL), CLOCK, and NPAS2
BMAL1 (ARNTL), CLOCK, and NPAS2, which acts redundantly with CLOCK, are key activators of diurnal circadian gene expression (reviewed in Cox and Takahashi 2019). Their expression is positively regulated by the Retinoid-related orphan receptors RORA, RORB, and RORC and negatively regulated by the nuclear receptor NR1D1 (REV-ERBA), all of which complete for the same ROR responsive elements (RRE, RORE) (inferred from mouse homologs in Ueda et al. 2002, Guilaumond et al. 2005) in the BMAL1 promoter (inferred from the mouse homolog in Sato et al. 2004, Akashi and Takumi 2005, Guillaumond et al. 2005, Takeda et al. 2012) and CLOCK promoter (inferred from mouse homologs in Lau et al. 2004, Takeda et al. 2012). ROR nuclear receptors bind oxysterols while NR1D1 binds heme, thus providing potential links with metabolism.
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ROR nuclear receptors recruit coactivators of transcription such as EP300 (p300), PPARGC1A (PGC1A) (inferred from mouse homologs in Lau et al. 2004), and NRIP1 to activate transcription by RNA polymerase II. In contrast, heme-bound NR1D1 recruits the corepressor NCOR1, and the histone deacetylase HDAC3 to repress transcription.
The genes encoding RORA, RORC, and NR1D1 regulate BMAL1 and CLOCK and are regulated by BMAL1 and CLOCK, thereby constituting a secondary loop in the mammalian circadian clock.
What the reference databases state
Statements
34 statements
34 statements · 1 reference database · Subject: Expression of BMAL (ARNTL), CLOCK, and NPAS2 · Sources: Reactome
- ATF2 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- BMAL1 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- CARM1 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- CHD9 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- CLOCK participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- CREBBP participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- CRTC1 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- CRTC2 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- CRTC3 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- EP300 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- HDAC3 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- HELZ2 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
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- MED1 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- MEF2C participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- MEF2D participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- NCOA1 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- NCOA2 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- NCOA6 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- NCOR1 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- NPAS2 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- NR1D1 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- NRIP1 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- PPARA participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- PPARGC1A participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- RAI1 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- RORA participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- RORB participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- RORC participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- RXRA participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- SIRT1 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- SMARCD3 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- TBL1X participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- TBL1XR1 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only
- TGS1 participates in Expression of BMAL (ARNTL), CLOCK, and NPAS2ProteinReactome R-HSA-9931509Inferred only