Gene Symbol: Nr1d1
Description: nuclear receptor subfamily 1, group D, member 1
Alias: REV-ERBAALPHA, nuclear receptor subfamily 1 group D member 1, EAR-1, V-erbA-related protein 1, V-erbA-related protein EAR-1, rev-erb alpha, rev-erbA-alpha
Species: rat
Products:     Nr1d1

Top Publications

  1. Duez H, van der Veen J, Duhem C, Pourcet B, Touvier T, Fontaine C, et al. Regulation of bile acid synthesis by the nuclear receptor Rev-erbalpha. Gastroenterology. 2008;135:689-98 pubmed publisher
    ..Here, we investigate a potential role for Rev-erbalpha in the control of bile acid metabolism via the regulation of the neutral bile acid synthesis pathway...
  2. Yin L, Wu N, Curtin J, Qatanani M, Szwergold N, Reid R, et al. Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways. Science. 2007;318:1786-9 pubmed
    ..Thus, Rev-erbalpha serves as a heme sensor that coordinates the cellular clock, glucose homeostasis, and energy metabolism. ..
  3. Schmutz I, Ripperger J, Baeriswyl Aebischer S, Albrecht U. The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors. Genes Dev. 2010;24:345-57 pubmed publisher
    ..The concept that PER2 may propagate clock information to metabolic pathways via nuclear receptors adds an important facet to the clock-dependent regulation of biological networks. ..
  4. Preitner N, Damiola F, Lopez Molina L, Zakany J, Duboule D, Albrecht U, et al. The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell. 2002;110:251-60 pubmed
    ..While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation. ..
  5. Yin L, Lazar M. The orphan nuclear receptor Rev-erbalpha recruits the N-CoR/histone deacetylase 3 corepressor to regulate the circadian Bmal1 gene. Mol Endocrinol. 2005;19:1452-9 pubmed
    ..These data demonstrate a new function for the N-CoR/HDAC3 complex in regulating the expression of genes involved in circadian rhythm by functioning as corepressor for Rev-erbalpha. ..
  6. Journiac N, Jolly S, Jarvis C, Gautheron V, Rogard M, Trembleau A, et al. The nuclear receptor ROR(alpha) exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes. Proc Natl Acad Sci U S A. 2009;106:21365-70 pubmed publisher
    ..Thus, our findings indicate that ROR(alpha) is a pluripotent molecular player in constitutive and adaptive astrocyte physiology. ..
  7. Le Martelot G, Claudel T, Gatfield D, Schaad O, Kornmann B, Lo Sasso G, et al. REV-ERBalpha participates in circadian SREBP signaling and bile acid homeostasis. PLoS Biol. 2009;7:e1000181 pubmed publisher
    ..In conclusion, our study suggests that rhythmic cholesterol and bile acid metabolism is not just driven by alternating feeding-fasting cycles, but also by REV-ERBalpha, a component of the circadian clockwork circuitry. ..
  8. Wang J, Lazar M. Bifunctional role of Rev-erbalpha in adipocyte differentiation. Mol Cell Biol. 2008;28:2213-20 pubmed publisher
    ..Thus, opposite to what might be predicted from Rev-erbalpha gene expression, Rev-erbalpha protein levels must rise and then fall for adipocyte differentiation to occur. ..
  9. Lazar M, Hodin R, Darling D, Chin W. A novel member of the thyroid/steroid hormone receptor family is encoded by the opposite strand of the rat c-erbA alpha transcriptional unit. Mol Cell Biol. 1989;9:1128-36 pubmed
    ..Potential implications of this unusual genomic arrangement are discussed. ..

More Information


  1. Zhao L, Isayama K, Chen H, Yamauchi N, Shigeyoshi Y, Hashimoto S, et al. The nuclear receptor REV-ERBα represses the transcription of growth/differentiation factor 10 and 15 genes in rat endometrium stromal cells. Physiol Rep. 2016;4: pubmed publisher
    ..Our results provide novel evidence regarding the functions of cellular oscillators regulating the expression of downstream genes during the differentiation of UESCs. ..
  2. Chen H, Isayama K, Kumazawa M, Zhao L, Yamauchi N, Shigeyoshi Y, et al. Integration of the nuclear receptor REV-ERBα linked with circadian oscillators in the expressions of Alas1, Ppargc1a, and Il6 genes in rat granulosa cells. Chronobiol Int. 2015;32:739-49 pubmed publisher
  3. Adelmant G, Begue A, Stehelin D, Laudet V. A functional Rev-erb alpha responsive element located in the human Rev-erb alpha promoter mediates a repressing activity. Proc Natl Acad Sci U S A. 1996;93:3553-8 pubmed
  4. Isayama K, Zhao L, Chen H, Yamauchi N, Shigeyoshi Y, Hashimoto S, et al. Removal of Rev-erbα inhibition contributes to the prostaglandin G/H synthase 2 expression in rat endometrial stromal cells. Am J Physiol Endocrinol Metab. 2015;308:E650-61 pubmed publisher
    ..Collectively, this study demonstrates that the attenuation of the circadian clock, especially its core component Rev-erbα, contributes to the induction of Ptgs2 during decidualization. ..
  5. Szántóová K, Zeman M, Veselá A, Herichova I. Effect of phase delay lighting rotation schedule on daily expression of per2, bmal1, rev-erb?, ppar?, and pdk4 genes in the heart and liver of Wistar rats. Mol Cell Biochem. 2011;348:53-60 pubmed publisher
    ..Expression of metabolic genes was influenced more in the liver than in the heart. Results indicate that frequent shifts of LD cycle may interfere with control of lipid metabolism. ..
  6. Li T, Eheim A, Klein S, Uschner F, Smith A, Brandon Warner E, et al. Novel role of nuclear receptor Rev-erb? in hepatic stellate cell activation: potential therapeutic target for liver injury. Hepatology. 2014;59:2383-96 pubmed publisher
    ..Our studies identify Rev-erb? as a novel regulator of HSC transdifferentiation and offers exciting new insights on the therapeutic potential of Rev-erb ligands. ..
  7. Tasaki H, Zhao L, Isayama K, Chen H, Yamauchi N, Shigeyoshi Y, et al. Inhibitory role of REV-ERBα in the expression of bone morphogenetic protein gene family in rat uterus endometrium stromal cells. Am J Physiol Cell Physiol. 2015;308:C528-38 pubmed publisher
    ..Collectively, these results indicate that the Bmp genes are upregulated by the attenuation of the cellular circadian clock; in particular, its core component REV-ERBα functions as a transcriptional silencer in the Bmp gene family. ..
  8. Vieira E, Marroquí L, Batista T, Caballero Garrido E, Carneiro E, Boschero A, et al. The clock gene Rev-erb? regulates pancreatic ?-cell function: modulation by leptin and high-fat diet. Endocrinology. 2012;153:592-601 pubmed publisher
    ..Although the increase in Rev-erb? expression may promote ?-cell adaptation in different metabolic situations, its deregulation may lead to altered ?-cell function. ..
  9. Fang M, Zhang X, Zarbl H. Methylselenocysteine resets the rhythmic expression of circadian and growth-regulatory genes disrupted by nitrosomethylurea in vivo. Cancer Prev Res (Phila). 2010;3:640-52 pubmed publisher
    ..These results suggest that dietary methylselenocysteine counteracted the disruptive effect of NMU on circadian expression of genes essential to normal mammary cell growth and differentiation. ..
  10. Poliandri A, Gamsby J, Christian M, Spinella M, Loros J, Dunlap J, et al. Modulation of clock gene expression by the transcriptional coregulator receptor interacting protein 140 (RIP140). J Biol Rhythms. 2011;26:187-99 pubmed publisher
    ..These results indicate that RIP140 is not only involved in metabolic control but also acts as a coactivator for ROR?, influencing clock gene expression. ..
  11. Jannini E, Mitsuhashi T, Nikodem V. Developmental expression of mRNAs from a rat C-erbA genomic locus. Biochem Biophys Res Commun. 1992;184:739-45 pubmed
    ..No functional results can be seen in vivo from potential anti sense pairing of Rev-erbA alpha with the variant. ..
  12. Novakova M, Polidarova L, Sladek M, Sumova A. Restricted feeding regime affects clock gene expression profiles in the suprachiasmatic nucleus of rats exposed to constant light. Neuroscience. 2011;197:65-71 pubmed publisher
  13. Hirota T, Kon N, Itagaki T, Hoshina N, Okano T, Fukada Y. Transcriptional repressor TIEG1 regulates Bmal1 gene through GC box and controls circadian clockwork. Genes Cells. 2010;15:111-21 pubmed publisher
    ..These findings highlight an active role of TIEG1 in the normal clock oscillation and GC box-mediated regulation of Bmal1 transcription. ..
  14. Spanjaard R, Nguyen V, Chin W. Rat Rev-erbA alpha, an orphan receptor related to thyroid hormone receptor, binds to specific thyroid hormone response elements. Mol Endocrinol. 1994;8:286-95 pubmed
    ..Our results indicate that Rev binds DNA with a different specificity than TR alpha-1 and might be involved in the regulation of a subset of thyroid hormone-regulated genes. ..
  15. Harding H, Lazar M. The orphan receptor Rev-ErbA alpha activates transcription via a novel response element. Mol Cell Biol. 1993;13:3113-21 pubmed
    ..Thus, Rev-Erb is a transcriptional activator whose properties differ dramatically from those of classical nuclear hormone receptors, including the TR encoded on the opposite strand of the same genomic locus. ..
  16. Fontaine C, Rigamonti E, Pourcet B, Duez H, Duhem C, Fruchart J, et al. The nuclear receptor Rev-erbalpha is a liver X receptor (LXR) target gene driving a negative feedback loop on select LXR-induced pathways in human macrophages. Mol Endocrinol. 2008;22:1797-811 pubmed publisher
    ..These data identify Rev-erbalpha as a new LXR target gene, inhibiting LXR-induction of TLR-4 in a negative transcriptional feedback loop, but not cholesterol homeostasis gene expression. ..
  17. Li H, Wang C, Hu J, Tan J. A study on circadian rhythm disorder of rat lung tissue caused by mechanical ventilation induced lung injury. Int Immunopharmacol. 2014;18:249-54 pubmed publisher
    ..Collectively, our findings are the first to show that REV-ERB? plays an important role in VILI and inflammation, and circadian rhythm disorder in inflammation response may be a novel pathogenesis of VILI. ..
  18. Xiao J, Zhou Y, Lai H, Lei S, Chi L, Mo X. Transcription factor NF-Y is a functional regulator of the transcription of core clock gene Bmal1. J Biol Chem. 2013;288:31930-6 pubmed publisher
    ..These results indicate that NF-Y is a functional activator of Bmal1 transcription and it cooperates with Sp1 and Rev-Erb? to generate the daily cycle of Bmal1 expression. ..
  19. Forman B, Chen J, Blumberg B, Kliewer S, Henshaw R, Ong E, et al. Cross-talk among ROR alpha 1 and the Rev-erb family of orphan nuclear receptors. Mol Endocrinol. 1994;8:1253-61 pubmed
    ..When coexpressed, both Rev-erb isoforms suppress the transcriptional activity of ROR alpha 1. Our data define Rev-erb and ROR/RZR as a family of related receptors with opposing activities on overlapping regulatory networks. ..
  20. Chen H, Chu G, Zhao L, Yamauchi N, Shigeyoshi Y, Hashimoto S, et al. Rev-erb? regulates circadian rhythms and StAR expression in rat granulosa cells as identified by the agonist GSK4112. Biochem Biophys Res Commun. 2012;420:374-9 pubmed publisher
    ..Our data are the first to show the Rev-erb? function in the steroid biosynthesis of rat granulosa cells, and to suggest that Rev-erb? may coordinate circadian rhythm and metabolism in rat ovaries. ..
  21. Hu J, Wang C. [Pulmonary expression of Nr1d1 in rats with ventilation-induced lung injury]. Nan Fang Yi Ke Da Xue Xue Bao. 2013;33:1544-6 pubmed
    To investigate the changes in the expression of nuclear receptor subfamily1 (Nr1d1) in the lungs of rats with ventilation-induced lung injury and explore the molecular mechanism...
  22. Chini C, Escande C, Nin V, Chini E. DBC1 (Deleted in Breast Cancer 1) modulates the stability and function of the nuclear receptor Rev-erbα. Biochem J. 2013;451:453-61 pubmed publisher
    ..In summary, our data identify DBC1 as an important regulator of the circadian receptor Rev-erbα and proposes that Rev-erbα could be involved in mediating some of the physiological effects of DBC1. ..
  23. Medici M, Ikram M, van der Lijn F, den Heijer T, Vernooij M, Hofman A, et al. The thyroid hormone receptor alpha locus and white matter lesions: a role for the clock gene REV-ERB?. Thyroid. 2012;22:1181-6 pubmed publisher
    ..05%, p=0.04; men: 0.05%±0.07%, p=0.80). Meta-analysis of the two populations showed that women lacking this haplotype have a 1.9 times larger WML volume (p=0.001). Our results suggest a role for REV-ERB? in the pathogenesis of WMLs. ..
  24. Meng Q, McMaster A, Beesley S, Lu W, Gibbs J, Parks D, et al. Ligand modulation of REV-ERBalpha function resets the peripheral circadian clock in a phasic manner. J Cell Sci. 2008;121:3629-35 pubmed publisher
    ..Therefore, similar regulation of REV-ERBalpha function by endogenous ligands, such as heme, is likely to be an important mechanism for clock resetting. In addition, we identify a new means to generate phasic shifts in the clock. ..
  25. Fontaine C, Dubois G, Duguay Y, Helledie T, Vu Dac N, Gervois P, et al. The orphan nuclear receptor Rev-Erbalpha is a peroxisome proliferator-activated receptor (PPAR) gamma target gene and promotes PPARgamma-induced adipocyte differentiation. J Biol Chem. 2003;278:37672-80 pubmed
    Rev-Erbalpha (NR1D1) is an orphan nuclear receptor encoded on the opposite strand of the thyroid receptor alpha gene...
  26. Gerhart Hines Z, Feng D, Emmett M, Everett L, Loro E, Briggs E, et al. The nuclear receptor Rev-erb? controls circadian thermogenic plasticity. Nature. 2013;503:410-413 pubmed publisher
    ..Here we show that the nuclear receptor Rev-erb? (also known as Nr1d1), a powerful transcriptional repressor, links circadian and thermogenic networks through the regulation of brown ..
  27. Zhang R, Yan C, Zhou X, Qian B, Li F, Sun Y, et al. Association of Rev-erb? in adipose tissues with Type 2 diabetes mellitus amelioration after gastric bypass surgery in Goto-Kakizaki rats. Am J Physiol Regul Integr Comp Physiol. 2013;305:R134-46 pubmed publisher
    ..The roles of Rev-erb? in adipose tissue were further investigated by observations of Rev-erb?-related molecules, with reference to previous reports. ..
  28. Valnegri P, Khelfaoui M, Dorseuil O, Bassani S, Lagneaux C, Gianfelice A, et al. A circadian clock in hippocampus is regulated by interaction between oligophrenin-1 and Rev-erb?. Nat Neurosci. 2011;14:1293-301 pubmed publisher