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Transcription Translation Feedback Loop
Transcription-translation feedback loop (TTFL), is a cellular model for explaining circadian rhythms in behavior and physiology. Widely conserved across species, the TTFL is auto-regulatory, in which transcription of clock genes is regulated by their own protein products. Discovery Circadian rhythms have been documented for centuries. For example, French astronomer Jean-Jacques d’Ortous de Mairan noted the periodic 24-hour movement of ''Mimosa'' plant leaves as early as 1729. However, science has only recently begun to uncover the cellular mechanisms responsible for driving observed circadian rhythms. The cellular basis of circadian rhythms is supported by the fact that rhythms have been observed in single-celled organisms Beginning in the 1970s, experiments conducted by Ron Konopka and colleagues, in which forward genetic methods were used to induce mutation, revealed that ''Drosophila melanogaster'' specimens with altered ''period'' (''Per'') genes also demonstrated altere ...
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Circadian Rhythm
A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., Endogeny (biology), endogenous) and responds to the environment (Entrainment (chronobiology), entrained by the environment). These 24-hour rhythms are driven by a circadian clock, and they have been widely observed in animals, plants, fungi and cyanobacteria. The term ''circadian'' comes from the Latin ''wikt:circa#Latin, circa'', meaning "approximately", and ''dies'', meaning "day". Processes with 24-hour cycles are more generally called diurnal rhythms; diurnal rhythms should not be called circadian rhythms unless they can be confirmed as endogenous, and not environmental. Although circadian rhythms are endogenous, they are adjusted to the local environment by external cues called zeitgebers (German for "time givers"), which include light, temperature and redox cy ...
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Cell Nucleus
The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have no nuclei, and a few others including osteoclasts have many. The main structures making up the nucleus are the nuclear envelope, a double membrane that encloses the entire organelle and isolates its contents from the cellular cytoplasm; and the nuclear matrix, a network within the nucleus that adds mechanical support. The cell nucleus contains nearly all of the cell's genome. Nuclear DNA is often organized into multiple chromosomes – long stands of DNA dotted with various proteins, such as histones, that protect and organize the DNA. The genes within these chromosomes are structured in such a way to promote cell function. The nucleus maintains the integrity of genes and controls the activities of the cell by regulating gene expres ...
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Cryptochrome
Cryptochromes (from the Greek κρυπτός χρώμα, "hidden colour") are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields in a number of species. The name ''cryptochrome'' was proposed as a ''portmanteau'' combining the '' chromatic'' nature of the photoreceptor, and the ''cryptogamic'' organisms on which many blue-light studies were carried out. The two genes ''Cry1'' and ''Cry2'' code the two cryptochrome proteins CRY1 and CRY2. In insects and plants, CRY1 regulates the circadian clock in a light-dependent fashion, whereas in mammals, CRY1 and CRY2 act as light-independent inhibitors of CLOCK-BMAL1 components of the circadian clock. In plants, blue-light photoreception can be used to cue developmental signals. Besides chlorophylls, cryptochromes are the only proteins known to form photoinduced radical-pairs ''in vivo''. These appear to enable some animal ...
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ARNTL
Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) or brain and muscle ARNT-Like 1 (BMAL1) is a protein that in humans is encoded by the gene on chromosome 11, region p15.3. It's also known as ''BMAL1'', ''MOP3'', and, less commonly, ''bHLHe5'', ''BMAL'', ''BMAL1C'', ''JAP3'', ''PASD3'', and ''TIC''. ''ARNTL'' encodes a transcription factor with a basic helix-loop-helix (bHLH) and two PAS domains. The human ''ARNTL'' gene has a predicted 24 exons, located on the p15 band of the 11th chromosome. The ARNTL protein is 626 amino acids long and plays a key role as one of the positive elements in the mammalian auto-regulatory transcription-translation negative feedback loop (TTFL), which is responsible for generating molecular circadian rhythms. Research has revealed that ''ARNTL'' is the only clock gene without which the circadian clock fails to function in humans. ''ARNTL'' has also been identified as a candidate gene for susceptibility to hypertension, diabetes, ...
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Circadian Clock Of Mammals
A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., endogenous) and responds to the environment ( entrained by the environment). These 24-hour rhythms are driven by a circadian clock, and they have been widely observed in animals, plants, fungi and cyanobacteria. The term ''circadian'' comes from the Latin ''circa'', meaning "approximately", and ''dies'', meaning "day". Processes with 24-hour cycles are more generally called diurnal rhythms; diurnal rhythms should not be called circadian rhythms unless they can be confirmed as endogenous, and not environmental. Although circadian rhythms are endogenous, they are adjusted to the local environment by external cues called zeitgebers (German for "time givers"), which include light, temperature and redox cycles. In clinical settings, an abnormal circadian rhythm in humans ...
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Circadian Clock Of Drosophila
A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., endogenous) and responds to the environment ( entrained by the environment). These 24-hour rhythms are driven by a circadian clock, and they have been widely observed in animals, plants, fungi and cyanobacteria. The term ''circadian'' comes from the Latin ''circa'', meaning "approximately", and ''dies'', meaning "day". Processes with 24-hour cycles are more generally called diurnal rhythms; diurnal rhythms should not be called circadian rhythms unless they can be confirmed as endogenous, and not environmental. Although circadian rhythms are endogenous, they are adjusted to the local environment by external cues called zeitgebers (German for "time givers"), which include light, temperature and redox cycles. In clinical settings, an abnormal circadian rhythm in humans ...
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Doubletime (gene)
Doubletime (dbt) also known as discs overgrown (dco) is a gene that encodes the double-time protein (DBT) in ''Drosophila melanogaster''. The double-time protein is a kinase that phosphorylates PER protein that regulates the molecularly-driven, biological clock controlling circadian rhythm. The mammalian homolog of doubletime is casein kinase I epsilon. Different mutations in the ''dbt'' gene have been shown to cause lengthening, shortening, or complete loss in period of locomotor activity in flies. Drosophila and certain vertebrate Casein Kinase Id shows circadian function that has been evolutionary conserved over long time spans. Discovery Double time gene (''dbt'') was first identified and characterized in 1998 by Michael Young and his team at The Rockefeller University. Young's research group, headed bJeffrey Price published their results in a paper which characterized three alleles of ''dbt'' in fruit flies. They discovered that two mutant alleles, named short and long ( ...
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E-box
An E-box (enhancer box) is a DNA response element found in some eukaryotes that acts as a protein-binding site and has been found to regulate gene expression in neurons, muscles, and other tissues. Its specific DNA sequence, CANNTG (where N can be any nucleotide), with a palindromic canonical sequence of CACGTG, is recognized and bound by transcription factors to initiate gene transcription. Once the transcription factors bind to the promoters through the E-box, other enzymes can bind to the promoter and facilitate transcription from DNA to mRNA. Discovery The E-box was discovered in a collaboration between Susumu Tonegawa's and Walter Gilbert's laboratories in 1985 as a control element in immunoglobulin heavy-chain enhancer. They found that a region of 140 base pairs in the tissue-specific transcriptional enhancer element was sufficient for different levels of transcription enhancement in different tissues and sequences. They suggested that proteins made by specific tissues acted ...
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CLOCK
A clock or a timepiece is a device used to measure and indicate time. The clock is one of the oldest human inventions, meeting the need to measure intervals of time shorter than the natural units such as the day, the lunar month and the year. Devices operating on several physical processes have been used over the millennia. Some predecessors to the modern clock may be considered as "clocks" that are based on movement in nature: A sundial shows the time by displaying the position of a shadow on a flat surface. There is a range of duration timers, a well-known example being the hourglass. Water clocks, along with the sundials, are possibly the oldest time-measuring instruments. A major advance occurred with the invention of the verge escapement, which made possible the first mechanical clocks around 1300 in Europe, which kept time with oscillating timekeepers like balance wheels., pp. 103–104., p. 31. Traditionally, in horology, the term ''clock'' was used for a stri ...
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Cycle (gene)
''Cycle'' (''cyc'') is a gene in ''Drosophila melanogaster'' that encodes the CYCLE protein (CYC). The ''Cycle'' gene ''(''c''yc)'' is expressed in a variety of cell types in a circadian manner. It is involved in controlling both the sleep-wake cycle and circadian regulation of gene expression by promoting transcription in a negative feedback mechanism. The c''yc'' gene is located on the left arm of chromosome 3 and codes for a transcription factor containing a basic helix-loop-helix (bHLH) domain and a PAS domain. The 2.17 kb c''yc'' gene is divided into 5 coding exons totaling 1,625 base pairs which code for 413 aminos acid residues. Currently 19 alleles are known for c''yc'' ., accessdate=10 April 2013 Orthologs performing the same function in other species include ARNTL and ARNTL2. Function ''Cycle'' is primarily known for its role in the genetic transcription-translation feedback loop that generates circadian rhythms in ''Drosophila''. In the cell nucleus, the CYCLE pr ...
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Timeless (gene)
Timeless (''tim'') is a gene in multiple species but is most notable for its role in ''Drosophila'' for encoding TIM, an essential protein that regulates circadian rhythm. ''Timeless'' mRNA and protein oscillate rhythmically with time as part of a transcription-translation negative feedback loop involving the '' period'' (''per'') gene and its protein. Discovery In 1994, ''timeless'' was discovered through forward genetic screening performed by Jeffery L. Price while working in the lab of Michael W. Young. This gene was found when they noticed an arrhythmic ''tim''01 mutant via a P element screen. The tim01 mutation caused arrhythmic behavior, defined by the lack of ability to establish proper circadian rhythms. In 1995, the timeless gene was cloned by Amita Sehgal and partners in the lab of Michael W. Young. Unlike the Drosophila ''timeless'' gene, homologs have been discovered in other species that are non-essential for circadian rhythm. The discovery of ''timeless'' foll ...
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Entrainment (chronobiology)
In the study of chronobiology, entrainment occurs when rhythmic physiological or behavioral events match their period to that of an environmental oscillation. It is ultimately the interaction between circadian rhythms and the environment. A central example is the entrainment of circadian rhythms to the daily light–dark cycle, which ultimately is determined by the Earth's rotation. Exposure to certain environmental stimuli will cue a phase shift, and abrupt change in the timing of the rhythm. Entrainment helps organisms maintain an adaptive phase relationship with the environment as well as prevent drifting of a free running rhythm. This stable phase relationship achieved is thought to be the main function of entrainment. There are two general modes of entrainment: phasic and continuous. The phasic mode is when there is limited interaction with the environment to "reset" the clock every day by the amount equal to the "error", which is the difference between the environmental cycle ...
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