Disease relevance of CLOCK

• With the role of Clock and Bmal1 in fertility becoming clearer, it may be time to pursue the effect of polymorphisms in these genes in relation to the various types of infertility in humans [1].
• The number of oxygen desaturation episodes exceeding 4% associated with defective delayed Recall of Logical Stories of the Wechsler Memory Scale and with spatial orientation (Clock test) in the habitual snorers' group even after adjusting for age and obesity [2].
• Lack of association between the 3092 T-->C Clock gene polymorphism and cluster headache [3].
• One hundred and seven CH patients, diagnosed according to the International Classification of Headache Disorders, 2nd Edition, (ICHD-II) criteria, and 210 healthy age, sex and ethnicity-matched controls were genotyped for the 3092 T-->C Clock gene polymorphism (also known as 3111 T-->C) [3].
• These results do not support Clock 3111C as a marker for diurnal preference, tau, or delayed sleep phase syndrome in humans [4].

Psychiatry related information on CLOCK

• We studied two SNPs in the Clock gene aiming to find any association with narcolepsy [5].
• Mutation screening of the human Clock gene in circadian rhythm sleep disorders [6].
• These were followed by Word List delayed recognition of foils and delayed recall, Consortium to Establish a Registry for Alzheimer's Disease Praxis, Clock Drawing, the Boston Naming Test, and Orientation, with rate ratios between 1.7 and 3.0 (P<.05) [7].
• METHODS: Clock drawings were obtained during the initial clinical assessments of 75 participants in a longitudinal study of healthy aging and dementia of the Alzheimer type (15 cognitively normal, 25 with very mild dementia, 21 with mild dementia, and 14 with moderate to severe dementia, as staged by the Clinical Dementia Rating) [8].
• MEASUREMENTS: Neuropsychological tests, dementia-related scales, and clock drawings rated by a new 20-item Clock Drawing Interpretation Scale [9].

High impact information on CLOCK

• The vasopressin RNA rhythm is abolished in the SCN of Clock/Clock animals, leading to markedly decreased peptide levels [10].
• The proteins Clock and Bmal1 form a heterodimer which activates the transcription of the Per gene from the E-box elements in its promoter region [11].
• Time for chronotherapy? Clock genes dictate sensitivity to cyclophosphamide [12].
• We present a computational model for the mammalian circadian clock based on the intertwined positive and negative regulatory loops involving the Per, Cry, Bmal1, Clock, and Rev-Erb alpha genes [13].
• Biological clock in total darkness: the Clock/MOP3 circadian system of the blind subterranean mole rat [14].

Biological context of CLOCK

• A recent report established a genetic linkage between narcolepsy and the chromosomal region 4p13-q21 that contains the Clock gene [5].
• We found in the 90% of gestation capuchin monkey fetus expression of the clock genes Bmal-1, Per-2, Cry-2, and Clock in the SCN, adrenal, pituitary, brown fat, and pineal [15].
• Hypothalamic circadian organization in birds. II. Clock gene expression [16].
• Furthermore, a study examining the association between Clock gene polymorphisms and insomnia revealed a higher recurrence of initial, middle, and terminal insomnia in patients homozygous for the Clock genotype [17].
• Here we describe the cloning, sequence, and expression of the circadian Clock and MOP3 cDNAs of the Spalax ehrenbergi superspecies in Israel. Both genes are relatively conserved, although characterized by a significant number of amino acid substitutions [14].

Anatomical context of CLOCK

• In this study, we indicate the daily expression of clock genes period (Per) 1, 2, 3, Bmal1, and Clock in whole blood cells in 12 healthy male subjects [18].
• In this article, we develop a mathematical formulation of a new version of the Clock and Wavefront model proposed by Pourquié and co-workers (Dubrulle, J., McGrew, M.J., Pourquié, O., 2001. FGF signalling controls somite boundary position and regulates segmentation clock control of spatiotemporal Hox gene activation. Cell 106, 219-232) [19].
• Using immunochemistry and biochemical subcellular fractionation, we have shown that Clock localizes to the Z-disk of the myofilaments [20].
• In this study, we determined some of the factors that regulate Clock expression and subcellular distribution in myocytes [20].
• The circadian protein Clock localizes to the sarcomeric Z-disk and is a sensor of myofilament cross-bridge activity in cardiac myocytes [20].

Associations of CLOCK with chemical compounds

• The endogenous circadian machinery involves positive and negative transcriptional feedback loops implicating different genes (particularly period (Per) 1-3, Clock, Bmal1, cryptochrome (Cry) 1-2) [21].
• In mammals the PAS transcription factors Clock, NPAS2, and BMAL1 regulate gene expression as a function of the day-night cycle [22].
• Nevertheless, the SCN of Clock(Delta19) + MEL mutant mice cannot maintain liver and muscle rhythmicity through rhythmic outputs, including melatonin secretion, in the absence of functional Clock expression in the tissues [23].
• We suggest that this reduction in transcriptional activity may be attributed to the Spalax Clock glutamine-rich domain, which is unique in its amino acid composition compared with other studied mammalian species [14].
• Improved Tumor Control through Circadian Clock Induction by Seliciclib, a Cyclin-Dependent Kinase Inhibitor [24].

Physical interactions of CLOCK

• Here we report that age alters the 24-h expression profile of Clock and its binding partner Bmal1 in the hamster SCN [25].

Other interactions of CLOCK

• However, despite multiple putative E-boxes in the MT(1) promoter, transfected Clock and Bmal1 were unable to regulate either basal or Pitx-1-stimulated MT(1) promoter activity [26].
• Other evidence derives from the relationship of circadian genes, NPAS2 and Clock, to metabolism [27].
• GIGANTEA Acts in Blue Light Signaling and Has Biochemically Separable Roles in Circadian Clock and Flowering Time Regulation [28].
• Effects of venlafaxine, an antidepressant acting by selective serotonin and norepinephrine reuptake inhibition with a potency ratio of 5:1, were assessed in a standardized, actual driving test, a battery of psychomotor tests (Critical Flicker/Fusion Frequency, Critical Tracking, Divided Attention), and a 45-minute vigilance test (Mackworth Clock) [29].
• We compared the expression of period and Clock genes in the head of the linden bug, Pyrrhocoris apterus, kept under diapause promoting short days (SD) and diapause-preventing long days (LD), using an RNase protection assay [30].

Analytical, diagnostic and therapeutic context of CLOCK

• The molecular cloning of this gene may lead to a better understanding of sleep mechanisms, as has been the case for circadian rhythms following the cloning of frq, per, and Clock [31].
• OBJECTIVE: To determine the validity and reliability of a rapidly administered neurocognitive screening battery consisting of 4 brief tests (Enhanced Cued Recall, Temporal Orientation, Verbal Fluency, and Clock Drawing) to distinguish between patients with probable Alzheimer's disease (AD) and healthy control subjects [32].
• Genomic organization of the rat Clock gene and sequence analysis in inbred rat strains [33].
• A detailed scoring system for qualitative as well as quantitative evaluation of Clock Drawing errors was used [34].
• MEASUREMENTS: Clock drawings; lipoprotein cholesterol levels; serum progesterone, estrone, estradiol, and steroid hormone binding globin levels; self-reported data on smoking, alcohol intake, prior medical diagnoses, and use of certain medications including hormone replacement therapy and analgesics [35].

References