2023
DOI: 10.1038/s41598-023-34115-w
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Prediction of mammalian tissue-specific CLOCK–BMAL1 binding to E-box DNA motifs

Abstract: The Brain and Muscle ARNTL-Like 1 protein (BMAL1) forms a heterodimer with either Circadian Locomotor Output Cycles Kaput (CLOCK) or Neuronal PAS domain protein 2 (NPAS2) to act as a master regulator of the mammalian circadian clock gene network. The dimer binds to E-box gene regulatory elements on DNA, activating downstream transcription of clock genes. Identification of transcription factor binding sites and genomic features that correlate to DNA binding by BMAL1 is a challenging problem, given that CLOCK–BM… Show more

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Cited by 7 publications
(5 citation statements)
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“…Notably, Ehlen et al discovered that skeletal muscle possesses regulatory capabilities over sleep, with mice exhibiting higher expression of the BMAL1 protein in muscle tissue demonstrating faster recovery from sleep deprivation ( 20 ). BMAL1 serves as a key clock control gene within the mammalian circadian clock gene network, regulating not only the sleep-wake cycle but also influencing behavioral performance ( 21 , 22 ). Furthermore, investigations have revealed a heightened risk of sleep apnea in individuals with muscular dystrophy (73% prevalence) ( 23 ).…”
Section: Discussionmentioning
confidence: 99%
“…Notably, Ehlen et al discovered that skeletal muscle possesses regulatory capabilities over sleep, with mice exhibiting higher expression of the BMAL1 protein in muscle tissue demonstrating faster recovery from sleep deprivation ( 20 ). BMAL1 serves as a key clock control gene within the mammalian circadian clock gene network, regulating not only the sleep-wake cycle but also influencing behavioral performance ( 21 , 22 ). Furthermore, investigations have revealed a heightened risk of sleep apnea in individuals with muscular dystrophy (73% prevalence) ( 23 ).…”
Section: Discussionmentioning
confidence: 99%
“… 48 The most enriched E-box is the preferred motif for the circadian regulator, BMAL1. 49 Notably, binding of BMAL1 and other members of the bHLH family are sensitive to DNA methylation, and circadian rhythm per se is associated with alterations in DNA methylation. 50 , 51 , 52 Abnormal circadian rhythm has been associated with perturbed inflammatory response, 53 , 54 and more recently, with PASC.…”
Section: Discussionmentioning
confidence: 99%
“…Part of the divergence between tissues may be an artifact of statistical underpowering or technical differences in rhythm detection algorithms (63,64). Tissue-specific enhancers and chromatin accessibility likely play a part (65)(66)(67). Yet, there likely exist additional regulatory layers that connect the clock to specific downstream effectors based on cellular context, particularly in pathologic states.…”
Section: Limitations Of the Clock Paradigmmentioning
confidence: 99%