arntl transcription factors


Summary: Basic helix-loop-helix (bHLH) domain-containing proteins that play important roles in CIRCADIAN RHYTHM regulation. They combine with CLOCK PROTEINS to form heterodimeric transcription factors that are specific for E-BOX ELEMENTS and stimulate the transcription of several E-box genes that are involved in cyclical regulation.

Top Publications

  1. Gustafson C, Parsley N, Asimgil H, Lee H, Ahlbach C, Michael A, et al. A Slow Conformational Switch in the BMAL1 Transactivation Domain Modulates Circadian Rhythms. Mol Cell. 2017;66:447-457.e7 pubmed publisher
    ..Furthermore, isomerization is regulated by the cyclophilin family of peptidyl-prolyl isomerases, highlighting the potential for regulation of BMAL1 protein dynamics in period determination. ..
  2. Dudek M, Gossan N, Yang N, Im H, Ruckshanthi J, Yoshitane H, et al. The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity. J Clin Invest. 2016;126:365-76 pubmed publisher
    ..Together, these results define a regulatory mechanism that links chondrocyte BMAL1 to the maintenance and repair of cartilage and suggest that circadian rhythm disruption is a risk factor for joint diseases such as OA. ..
  3. Kiessling S, Beaulieu Laroche L, Blum I, Landgraf D, Welsh D, Storch K, et al. Enhancing circadian clock function in cancer cells inhibits tumor growth. BMC Biol. 2017;15:13 pubmed publisher
    ..Thus, our work reveals that enhancing circadian clock function might represent a novel strategy to control cancer progression. ..
  4. Frederick A, Goldsmith J, de Zavalía N, Amir S. Mapping the co-localization of the circadian proteins PER2 and BMAL1 with enkephalin and substance P throughout the rodent forebrain. PLoS ONE. 2017;12:e0176279 pubmed publisher
    ..These results indicate that clock genes are not unique to specific cell types, and further studies will be required to determine the factors that contribute to the regulation of clock gene expression throughout the brain. ..
  5. Cubuk C, Markowsky H, Herwig A. Hypothalamic control systems show differential gene expression during spontaneous daily torpor and fasting-induced torpor in the Djungarian hamster (Phodopus sungorus). PLoS ONE. 2017;12:e0186299 pubmed publisher
    ..This should be carefully taken into account when interpreting data in torpor research, especially from animal models of fasting-induced hypometabolism such as mice. ..
  6. Lin R, Mo Y, Zha H, Qu Z, Xie P, Zhu Z, et al. CLOCK Acetylates ASS1 to Drive Circadian Rhythm of Ureagenesis. Mol Cell. 2017;68:198-209.e6 pubmed publisher
    ..Taken together, CLOCK modulates metabolic rhythmicity by acting as a rhythmic acetyl-transferase for metabolic enzymes. ..
  7. Aryal R, Kwak P, Tamayo A, Gebert M, Chiu P, Walz T, et al. Macromolecular Assemblies of the Mammalian Circadian Clock. Mol Cell. 2017;67:770-782.e6 pubmed publisher
    ..Our results define the macromolecular assemblies comprising the circadian feedback loop and provide an initial structural view of endogenous eukaryotic clock machinery. ..
  8. Narasimamurthy R, Virshup D. A Flick of the Tail Keeps the Circadian Clock in Line. Mol Cell. 2017;66:437-438 pubmed publisher
    ..In this issue of Molecular Cell, Gustafson et al. (2017) report an additional requirement for accurate timekeeping, a cis/trans conformational flicker in the transcriptional activation domain of the core clock protein BMAL1. ..
  9. Bhatwadekar A, Beli E, Diao Y, Chen J, Luo Q, Alex A, et al. Conditional Deletion of Bmal1 Accentuates Microvascular and Macrovascular Injury. Am J Pathol. 2017;187:1426-1435 pubmed publisher

More Information


  1. Namihira M, Honma S, Abe H, Tanahashi Y, Ikeda M, Honma K. Daily variation and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the pineal body and different areas of brain in rats. Neurosci Lett. 1999;267:69-72 pubmed
    ..The BMAL1 expressions in these areas were similar to the case in the pineal. These findings indicate that the mammalian clock gene, Clock and BMAL1, are expressed differently in the different areas of the brain and the pineal. ..
  2. Gerstner J. The aging clock: to 'BMAL'icious toward learning and memory. Aging (Albany NY). 2010;2:251-4 pubmed
  3. Sharp B, Paquet E, Naef F, Bafna A, Wijnen H. A new promoter element associated with daily time keeping in Drosophila. Nucleic Acids Res. 2017;45:6459-6470 pubmed publisher
    ..Nevertheless, our results indicate that CATAC's enhancer function persists in the absence of CLK/CYC. Thus, CATAC represents a novel cis-regulatory element encoding clock-controlled regulation. ..
  4. Sobel J, Krier I, Andersin T, Raghav S, Canella D, Gilardi F, et al. Transcriptional regulatory logic of the diurnal cycle in the mouse liver. PLoS Biol. 2017;15:e2001069 pubmed publisher
    ..Together, our temporal DNase I mappings allowed us to decipher the global regulation of diurnal transcription rhythms in the mouse liver. ..
  5. Fahrenkrug J, Georg B, Hannibal J, Jørgensen H. Hypophysectomy abolishes rhythms in rat thyroid hormones but not in the thyroid clock. J Endocrinol. 2017;233:209-216 pubmed publisher
    ..Our findings indicate that the daily rhythm of thyroid hormone secretion is governed by SCN signalling via the rhythmic TSH secretion rather than by the local thyroid clock, which was still ticking after hypophysectomy. ..
  6. Fan Z, Zhao M, Joshi P, Li P, Zhang Y, Guo W, et al. A class of circadian long non-coding RNAs mark enhancers modulating long-range circadian gene regulation. Nucleic Acids Res. 2017;45:5720-5738 pubmed publisher
    ..Our results suggest that the enhancer-associated circadian lncRNAs mark the genomic loci modulating long-range circadian gene regulation and shed new lights on the evolutionary origin of lncRNAs. ..
  7. Stevanovic K, Yunus A, Joly Amado A, Gordon M, Morgan D, Gulick D, et al. Disruption of normal circadian clock function in a mouse model of tauopathy. Exp Neurol. 2017;294:58-67 pubmed publisher
    ..Furthermore, these results establish the Tg4510 mouse line as a model to study how tauopathy disrupts normal circadian rhythm biology. ..
  8. Jiang N, Wang Z, Cao J, Dong Y, Chen Y. Effect of monochromatic light on circadian rhythmic expression of clock genes in the hypothalamus of chick. J Photochem Photobiol B. 2017;173:476-484 pubmed publisher
    ..Our results also suggest that the circadian clock in the chick hypothalamus such as non-SCN brain region were involved in the regulation of photo information. ..
  9. Musiek E, Lim M, Yang G, Bauer A, Qi L, Lee Y, et al. Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration. J Clin Invest. 2013;123:5389-400 pubmed publisher
    ..Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration. ..
  10. Børglum A, Demontis D, Grove J, Pallesen J, Hollegaard M, Pedersen C, et al. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci. Mol Psychiatry. 2014;19:325-33 pubmed publisher
    ..3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies. ..
  11. Robinson R. Chronos: stress makes the clock tick. PLoS Biol. 2014;12:e1001838 pubmed publisher
  12. Rybakowski J, Dmitrzak Weglar M, Kliwicki S, Hauser J. Polymorphism of circadian clock genes and prophylactic lithium response. Bipolar Disord. 2014;16:151-8 pubmed
    ..Of special interest may be polymorphisms of these genes involved both in the predisposition to bipolar mood disorder and the lithium response. ..
  13. Sato F, Kohsaka A, Takahashi K, Otao S, Kitada Y, Iwasaki Y, et al. Smad3 and Bmal1 regulate p21 and S100A4 expression in myocardial stromal fibroblasts via TNF-?. Histochem Cell Biol. 2017;148:617-624 pubmed publisher
    ..This new evidence suggests that Smad3 and Bmal1 regulate p21 and S100A4 expression in myocardial stromal fibroblasts through TNF-?. ..
  14. Schallner N, Lieberum J, Gallo D, LeBlanc R, Fuller P, Hanafy K, et al. Carbon Monoxide Preserves Circadian Rhythm to Reduce the Severity of Subarachnoid Hemorrhage in Mice. Stroke. 2017;48:2565-2573 pubmed publisher
    ..Exposure to CO rescues the loss of HO-1 and thus merits further investigation in patients with SAH. ..
  15. Nakazato R, Kawabe K, Yamada D, Ikeno S, Mieda M, Shimba S, et al. Disruption of Bmal1 Impairs Blood-Brain Barrier Integrity via Pericyte Dysfunction. J Neurosci. 2017;37:10052-10062 pubmed publisher
    ..Our present study demonstrates the involvement of circadian clock component Bmal1 in BBB homeostasis and highlights the role of Bmal1 dysfunction in multiple neurological diseases. ..