{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNR1D1, also known as Rev‐erbα, is a pivotal orphan nuclear receptor within the core circadian clock machinery. It functions as a transcriptional repressor by binding heme as its physiological ligand and recruiting nuclear receptor corepressor complexes to regulate the rhythmic expression of key clock genes such as BMAL1, CLOCK, and NPAS2. Its protein stability is dynamically controlled by post‐translational modifications and ubiquitin–proteasome–mediated degradation, ensuring proper circadian periodicity and synchronization with environmental cues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in clock regulation, NR1D1 is intimately involved in metabolic homeostasis. It modulates hepatic glucose production by repressing genes such as Glc-6-Pase and PEPCK in response to signals from energy flux (for example, via apoA-IV), and it influences lipid metabolism and adipocyte differentiation through interactions with PPARγ and other metabolic pathways. Changes in NR1D1 activity have been implicated in the development of obesity and aberrant lipid profiles, reflecting its essential role in coordinating circadian and metabolic networks."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic and pharmacological investigations have further linked NR1D1 to mood and behavioral disorders. Variants in the NR1D1 gene and associated circadian networks contribute to susceptibility to bipolar disorder and major depressive disorder, and alterations in its expression or stability (for example, following lithium treatment) can disrupt circadian rhythmicity, thereby influencing mood regulation and treatment responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, NR1D1 exerts significant anti‐inflammatory and immunomodulatory functions. By repressing proinflammatory cytokine and matrix metalloproteinase gene expression, it helps limit synovial inflammation and cartilage degradation in disorders such as rheumatoid arthritis, while in lung and macrophage biology its activity contributes to reduced inflammatory responses and improved resolution of tissue injury."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "27", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also implicates NR1D1 in oncogenesis. In breast cancer models, altered NR1D1 expression impacts DNA repair mechanisms and modulates cellular responses to chemotherapeutic agents, thereby influencing tumor cell survival, aggressiveness, and potentially serving as a prognostic marker for treatment outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, detailed mechanistic studies have unraveled additional layers of NR1D1 regulation. Structural analyses have identified unique domains—including unconventional nuclear localization signals and distinctive ligand-binding interfaces—that mediate its interactions with other nuclear receptors (such as RORα) and corepressors. These findings extend NR1D1’s functional repertoire to include roles in endometrial regulation, osteoarthritis pathophysiology, and even the modulation of vascular and aortic remodeling processes, highlighting its broad impact on tissue-specific gene regulation and diverse disease states."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "34", "end_ref": "42"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lei Yin, Mitchell A Lazar "}, {"type": "b", "children": [{"type": "t", "text": "The orphan nuclear receptor Rev-erbalpha recruits the N-CoR/histone deacetylase 3 corepressor to regulate the circadian Bmal1 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2005-0057"}], "href": "https://doi.org/10.1210/me.2005-0057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15761026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15761026"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lei Yin, Nan Wu, Joshua C Curtin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1150179"}], "href": "https://doi.org/10.1126/science.1150179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18006707"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18006707"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Srilatha Raghuram, Keith R Stayrook, Pengxiang Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REV-ERBbeta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb1344"}], "href": "https://doi.org/10.1038/nsmb1344"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18037887"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18037887"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Virginia Soria, Erika Martínez-Amorós, Geòrgia Escaramís, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropsychopharmacology (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/npp.2009.230"}], "href": "https://doi.org/10.1038/npp.2009.230"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20072116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20072116"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Christine Crumbley, Yongjun Wang, Douglas J Kojetin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the core mammalian clock component, NPAS2, as a REV-ERBalpha/RORalpha target gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.129288"}], "href": "https://doi.org/10.1074/jbc.M110.129288"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20817722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20817722"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Christine Crumbley, Thomas P Burris "}, {"type": "b", "children": [{"type": "t", "text": "Direct regulation of CLOCK expression by REV-ERB."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0017290"}], "href": "https://doi.org/10.1371/journal.pone.0017290"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21479263"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21479263"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kamila Weissová, Jitka Škrabalová, Kateřina Skálová, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circadian rhythms of melatonin and peripheral clock gene expression in idiopathic REM sleep behavior disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sleep Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.sleep.2018.07.019"}], "href": "https://doi.org/10.1016/j.sleep.2018.07.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30195196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30195196"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hervé Coste, Joan C Rodríguez "}, {"type": "b", "children": [{"type": "t", "text": "Orphan nuclear hormone receptor Rev-erbalpha regulates the human apolipoprotein CIII promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M203421200"}], "href": "https://doi.org/10.1074/jbc.M203421200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12021280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12021280"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Coralie Fontaine, Guillaume Dubois, Yannick Duguay, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The orphan nuclear receptor Rev-Erbalpha is a peroxisome proliferator-activated receptor (PPAR) gamma target gene and promotes PPARgamma-induced adipocyte differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M304664200"}], "href": "https://doi.org/10.1074/jbc.M304664200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12821652"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12821652"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Hélène Duez, Bart Staels "}, {"type": "b", "children": [{"type": "t", "text": "Rev-erb-alpha: an integrator of circadian rhythms and metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Appl Physiol (1985) (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/japplphysiol.00570.2009"}], "href": "https://doi.org/10.1152/japplphysiol.00570.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19696364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19696364"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Nan Wu, Lei Yin, Elyisha A Hanniman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Negative feedback maintenance of heme homeostasis by its receptor, Rev-erbalpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1825809"}], "href": "https://doi.org/10.1101/gad.1825809"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19710360"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19710360"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Antonis Kourtidis, Ritu Jain, Richard D Carkner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An RNA interference screen identifies metabolic regulators NR1D1 and PBP as novel survival factors for breast cancer cells with the ERBB2 signature."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-09-1550"}], "href": "https://doi.org/10.1158/0008-5472.CAN-09-1550"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20160030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20160030"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Xiaoming Li, Min Xu, Fei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Apolipoprotein A-IV reduces hepatic gluconeogenesis through nuclear receptor NR1D1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.511766"}], "href": "https://doi.org/10.1074/jbc.M113.511766"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24311788"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24311788"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Elaine Vieira, Elena g Ruano, Ana Lucia C Figueroa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered clock gene expression in obese visceral adipose tissue is associated with metabolic syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0111678"}], "href": "https://doi.org/10.1371/journal.pone.0111678"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25365257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25365257"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Alexandre Berthier, Manjula Vinod, Geoffrey Porez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combinatorial regulation of hepatic cytoplasmic signaling and nuclear transcriptional events by the OGT/REV-ERBα complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1805397115"}], "href": "https://doi.org/10.1073/pnas.1805397115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30397120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30397120"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Elena G Ruano, Silvia Canivell, Elaine Vieira "}, {"type": "b", "children": [{"type": "t", "text": "REV-ERB ALPHA polymorphism is associated with obesity in the Spanish obese male population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0104065"}], "href": "https://doi.org/10.1371/journal.pone.0104065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25089907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25089907"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Lei Yin, Jing Wang, Peter S Klein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1121613"}], "href": "https://doi.org/10.1126/science.1121613"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16484495"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16484495"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Jiajun Shi, Jacqueline K Wittke-Thompson, Judith A Badner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clock genes may influence bipolar disorder susceptibility and dysfunctional circadian rhythm."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.30714"}], "href": "https://doi.org/10.1002/ajmg.b.30714"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18228528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18228528"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Taro Kishi, Tsuyoshi Kitajima, Masashi Ikeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association analysis of nuclear receptor Rev-erb alpha gene (NR1D1) with mood disorders in the Japanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neures.2008.08.008"}], "href": "https://doi.org/10.1016/j.neures.2008.08.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18804497"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18804497"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Giovanni Severino, Mirko Manchia, Paolo Contu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association study in a Sardinian sample between bipolar disorder and the nuclear receptor REV-ERBalpha gene, a critical component of the circadian clock system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bipolar Disord (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-5618.2009.00667.x"}], "href": "https://doi.org/10.1111/j.1399-5618.2009.00667.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19267705"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19267705"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Mirko Manchia, Alessio Squassina, Donatella Congiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interacting genes in lithium prophylaxis: preliminary results of an exploratory analysis on the role of DGKH and NR1D1 gene polymorphisms in 199 Sardinian bipolar patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2009.10.003"}], "href": "https://doi.org/10.1016/j.neulet.2009.10.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19818381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19818381"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Hader A Mansour, Michael E Talkowski, Joel Wood, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bipolar Disord (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-5618.2009.00756.x"}], "href": "https://doi.org/10.1111/j.1399-5618.2009.00756.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19839995"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19839995"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Sara Campos-de-Sousa, Camila Guindalini, Leonardo Tondo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear receptor rev-erb-{alpha} circadian gene variants and lithium carbonate prophylaxis in bipolar affective disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Rhythms (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0748730410362713"}], "href": "https://doi.org/10.1177/0748730410362713"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20348464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20348464"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Siddheshwar J Utge, Pia Soronen, Anu Loukola, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0009259"}], "href": "https://doi.org/10.1371/journal.pone.0009259"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20174623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20174623"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Timo Partonen "}, {"type": "b", "children": [{"type": "t", "text": "Clock gene variants in mood and anxiety disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neural Transm (Vienna) (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00702-012-0810-2"}], "href": "https://doi.org/10.1007/s00702-012-0810-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22538398"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22538398"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Yin-Chieh Lai, Chung-Feng Kao, Mong-Liang Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Investigation of associations between NR1D1, RORA and RORB genes and bipolar disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0121245"}], "href": "https://doi.org/10.1371/journal.pone.0121245"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25789810"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25789810"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Vemika Chandra, Sahil Mahajan, Ankita Saini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human IL10 gene repression by Rev-erbα ameliorates Mycobacterium tuberculosis clearance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.455915"}], "href": "https://doi.org/10.1074/jbc.M113.455915"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23449984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23449984"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Ting Li, Ashley L Eheim, Sabine Klein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel role of nuclear receptor Rev-erbα in hepatic stellate cell activation: potential therapeutic target for liver injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.27049"}], "href": "https://doi.org/10.1002/hep.27049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24497272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24497272"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Isaac K Sundar, Kahkashan Rashid, Michael T Sellix, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The nuclear receptor and clock gene REV-ERBα regulates cigarette smoke-induced lung inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.09.157"}], "href": "https://doi.org/10.1016/j.bbrc.2017.09.157"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28974420"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28974420"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Weijie Zhao, Liyuan Cui, Xixi Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of Rev-erbα attenuates lipopolysaccharide-induced inflammatory reactions in human endometrial stroma cells via suppressing TLR4-regulated NF-κB activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Biochim Biophys Sin (Shanghai) (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/abbs/gmz078"}], "href": "https://doi.org/10.1093/abbs/gmz078"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31411318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31411318"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Hui Liu, Yuanli Zhu, Yutong Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-020-2314-6"}], "href": "https://doi.org/10.1038/s41419-020-2314-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32071294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32071294"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Na-Lee Ka, Tae-Young Na, Hyelin Na, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NR1D1 Recruitment to Sites of DNA Damage Inhibits Repair and Is Associated with Chemosensitivity of Breast Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-16-2099"}], "href": "https://doi.org/10.1158/0008-5472.CAN-16-2099"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28249904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28249904"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Hyelin Na, Jinil Han, Na-Lee Ka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High expression of NR1D1 is associated with good prognosis in triple-negative breast cancer patients treated with chemotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13058-019-1197-x"}], "href": "https://doi.org/10.1186/s13058-019-1197-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31779659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31779659"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "S Chopin-Delannoy, S Thénot, F Delaunay, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A specific and unusual nuclear localization signal in the DNA binding domain of the Rev-erb orphan receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Endocrinol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1677/jme.0.0300197"}], "href": "https://doi.org/10.1677/jme.0.0300197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12683943"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12683943"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "P Chaturvedi, M Pratta, K Steplewski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional characterization of an orphan nuclear receptor, Rev-ErbAalpha, in chondrocytes and its potential role in osteoarthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/art.22170"}], "href": "https://doi.org/10.1002/art.22170"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17075855"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17075855"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Daniel F Kripke, Farhad F Shadan, Arthur Dawson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genotyping sleep disorders patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Psychiatry Investig (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4306/pi.2010.7.1.36"}], "href": "https://doi.org/10.4306/pi.2010.7.1.36"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20396431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20396431"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Caroline A Phelan, Robert T Gampe, Millard H Lambert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of Rev-erbalpha bound to N-CoR reveals a unique mechanism of nuclear receptor-co-repressor interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.1860"}], "href": "https://doi.org/10.1038/nsmb.1860"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20581824"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20581824"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Fumiko Zenri, Hisahiko Hiroi, Mikio Momoeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of retinoic acid-related orphan receptor alpha and its responsive genes in human endometrium regulated by cholesterol sulfate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Steroid Biochem Mol Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jsbmb.2011.10.001"}], "href": "https://doi.org/10.1016/j.jsbmb.2011.10.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22024429"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22024429"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Claudia C S Chini, Carlos Escande, Veronica Nin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DBC1 (Deleted in Breast Cancer 1) modulates the stability and function of the nuclear receptor Rev-erbα."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20121085"}], "href": "https://doi.org/10.1042/BJ20121085"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23398316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23398316"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Jason P DeBruyne, Julie E Baggs, Trey K Sato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin ligase Siah2 regulates RevErbα degradation and the mammalian circadian clock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1501204112"}], "href": "https://doi.org/10.1073/pnas.1501204112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26392558"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26392558"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Stefano Rizza, Alessio Luzi, Maria Mavilio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alterations in Rev-ERBα/BMAL1 ratio and glycated hemoglobin in rotating shift workers: the EuRhythDia study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Diabetol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00592-021-01676-z"}], "href": "https://doi.org/10.1007/s00592-021-01676-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33788000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33788000"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Ling-Yue Sun, Yu-Yan Lyu, Heng-Yuan Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear Receptor NR1D1 Regulates Abdominal Aortic Aneurysm Development by Targeting the Mitochondrial Tricarboxylic Acid Cycle Enzyme Aconitase-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.121.057623"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.121.057623"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35880522"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35880522"}]}]}]}