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Expression of BMAL (ARNTL), CLOCK, and NPAS2
Summary
- Organism
- Homo sapiens (human)
- Reactome
- R-HSA-9931509
- PubChem
- R-HSA-9931509
- Description
-
- 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 (Wang et al. 2010) while NR1D1 binds heme (Yin et al. 2007, Raghuram et al. 2007), thus providing potential links with metabolism.
ROR nuclear receptors recruit coactivators of transcription such as EP300 (p300), PPARGC1A (PGC1A) (inferred from mouse homologs in Lau et al. 2004), and NRIP1 (Poliandri et al. 2011) to activate transcription by RNA polymerase II. In contrast, heme-bound NR1D1 recruits the corepressor NCOR1, and the histone deacetylase HDAC3 to repress transcription (Wu et al. 2009).
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.
- 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 (Wang et al. 2010) while NR1D1 binds heme (Yin et al. 2007, Raghuram et al. 2007), thus providing potential links with metabolism.
Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.
| UniProt ID | Protein Name | Gene Symbol | Pathway Viewer |
|---|---|---|---|
| O00327 | Basic helix-loop-helix ARNT-like protein 1 |
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| O15379 | Histone deacetylase 3 |
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| O15516 | Circadian locomoter output cycles protein kaput |
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| O60907 | F-box-like/WD repeat-containing protein TBL1X |
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| O75376 | Nuclear receptor corepressor 1 |
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| P15336 | Cyclic AMP-dependent transcription factor ATF-2 |
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| P35398 | Nuclear receptor ROR-alpha |
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| P48552 | Nuclear receptor-interacting protein 1 |
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| Q06413 | Myocyte-specific enhancer factor 2C |
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| Q09472 | Histone acetyltransferase p300 |
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