84-5275-08　PER2 200ul　526859

特徴

• Transcriptional repressor which forms a core component of the circadian clock.
• The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior.
• It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function.
• Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system.
• Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers').
• The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN.
• The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle.
• Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day.
• Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle).
• A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively.
• Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndrome and aging.
• A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism.
• Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters.
• The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression.
• This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively.
• PER1 and PER2 proteins transport CRY1 and CRY2 into the nucleus with appropriate circadian timing, but also contribute directly to repression of clock-controlled target genes through interaction with several classes of RNA-binding proteins, helicases and others transcriptional repressors.
• PER appears to regulate circadian control of transcription by at least three different modes.
• First, interacts directly with the CLOCK-ARTNL/BMAL1 at the tail end of the nascent transcript peak to recruit complexes containing the SIN3-HDAC that remodel chromatin to repress transcription.
• Second, brings H3K9 methyltransferases such as SUV39H1 and SUV39H2 to the E-box elements of the circadian target genes, like PER2 itself or PER1.
• The recruitment of each repressive modifier to the DNA seems to be very precisely temporally orchestrated by the large PER complex, the deacetylases acting before than the methyltransferases.
• Additionally, large PER complexes are also recruited to the target genes 3' termination site through interactions with RNA-binding proteins and helicases that may play a role in transcription termination to regulate transcription independently of CLOCK-ARTNL/BMAL1 interactions.
• Recruitment of large PER complexes to the elongating polymerase at PER and CRY termination sites inhibited SETX action, impeding RNA polymerase II release and thereby repressing transcriptional reinitiation.
• May propagate clock information to metabolic pathways via the interaction with nuclear receptors.
• Coactivator of PPARA and corepressor of NR1D1, binds rhythmically at the promoter of nuclear receptors target genes like ARNTL or G6PC.
• Directly and specifically represses PPARG proadipogenic activity by blocking PPARG recruitment to target promoters and thereby inhibiting transcriptional activation.
• Required for fatty acid and lipid metabolism, is involved as well in the regulation of circulating insulin levels.
• Plays an important role in the maintenance of cardiovascular functions through the regulation of NO and vasodilatatory prostaglandins production in aortas.
• Controls circadian glutamate uptake in synaptic vesicles through the regulation of VGLUT1 expression.
• May also be involved in the regulation of inflammatory processes.
• Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1 and ATF4.
• Negatively regulates the formation of the TIMELESS-CRY1 complex by competing with TIMELESS for binding to CRY1.
• Applications:Suitable for use in Western Blot, Immunohistochemistry, Immunofluorescence/Immunocytochemistry and ELISA.
• Other applications not tested.
• Recommended Dilution:Western Blot: 1:500-1:2000, incubate membrane with diluted antibody in TBS, 5% milk, 0.1% Tween20 at 4°C with gentle shaking, overnight
• Immunohistochemistry: 1:50-1:200Immunofluorescence (IF-IC): 1:100-1:500ELISA (peptide): 1:20,000-1:40,000Optimal dilutions to be determined by the researcher.
• Storage and Stability:May be stored at 4°C for short-term only.
• Aliquot to avoid repeated freezing and thawing.
• Store at -20°C.
• Aliquots are stable for 12 months after receipt.
• For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.