Summary of PER1
Per1 is an important circadian protein that influences blood sugar levels, cancer and some neurodegenerative conditions.
The Function of PER1
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 syndromes 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. Regulates circadian target genes expression at post-transcriptional levels, but may not be required for the repression at transcriptional level. Controls PER2 protein decay. Represses CRY2 preventing its repression on CLOCK/ARNTL target genes such as FXYD5 and SCNN1A in kidney and PPARA in liver. Besides its involvement in the maintenance of the circadian clock, has an important function in the regulation of several processes. Participates in the repression of glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) by ARNTL:CLOCK. Plays a role in the modulation of the neuroinflammatory state via the regulation of inflammatory mediators release, such as CCL2 and IL6. In spinal astrocytes, negatively regulates the MAPK14/p38 and MAPK8/JNK MAPK cascades as well as the subsequent activation of NFkappaB. Coordinately regulates the expression of multiple genes that are involved in the regulation of renal sodium reabsorption. Can act as gene expression activator in a gene and tissue specific manner, in kidney enhances WNK1 and SLC12A3 expression in collaboration with CLOCK. Modulates hair follicle cycling. Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1.
Protein names
Recommended name:
Period circadian protein homolog 1Alternative name(s):
hPER1Circadian clock protein PERIOD 1
Circadian pacemaker protein Rigui
- RS2735611 (PER1) ??
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Top Gene-Substance Interactions
PER1 Interacts with These Diseases
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Fixes
Methods to increase per 1 levels:
- Light Therapy: Exposure to bright light (10,000 lux for at least half an hour) upon waking up, preferably from natural light, can help shift one’s sleep schedule earlier [R1, R2].
- Dark Therapy: Limit light exposure before bedtime, especially exposure to the blue light from TV’s, computers, and phones, which can be done using blue-blocking glasses [R].
- Increased intake of Forskolin [R].
Substances That Increase PER1
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Substances That Decrease PER1
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Advanced Summary
The period circadian clock 1 gene, part of the Period gene family [R].
The Per1 gene encodes for the period circadian protein homolog 1 (per1 protein) [R].
The gene is involved in controlling the biological 24-hour clock known as circadian rhythm [R].
Per1 controls the circadian rhythm in the absence of light, but it can be shifted or changed with light exposure [R]. When exposed to light at night, the amount of the protein encoded for by Per1 increases [R].
The circadian rhythm influences behavior timing, including when you are awake and asleep, and has been correlated with certain diseases, such as diabetes, Parkinson’s disease, and certain cancers. It has also been shown to influence time of death [R1, R2].
Per1 production is observed mostly in the Suprachiasmatic nucleus (SCN) in the brain. Per1 production is also seen in other body tissues, at generally decreased levels, and with shifted cycles. [R]
Mutations in the Per1 gene show a shortened clock period of 23 hours, and can predispose one to accidents, low productivity, and decreased precision and stability [R1, R2].
Per1 helps integrate stress response with the circadian cycle, and changes in the gene can lead to increased alcohol consumption due to stress [R].
Mice with mutated Per1 genes showed altered phases of activity and body temperatures [R]
The Per1 protein is produced in a 24-hour cycle, where peaks in production are correlated with peaks in activity.
Other proteins trigger an increase in the production of the Per1 protein when concentrations are low. The Per1 protein causes a decrease in the production of itself (negative feedback) at high concentrations. This feedback cycle that takes about 24 hours. [R].
This gene is seen in most mammals and many insects, so it is highly conserved [R].
Mutant variations of the Per1 gene have been associated with certain cancers, including breast and prostate cancer [R]. These cancers show a decrease in Per1 protein production [R].
Decreasing Per1 in tumor cells leads to an increase in tumor cell growth, indicating that Per1 has a role in controlling the cell growth and reproduction cycle [R].
Increased Per1 can cause DNA damage and lead to programmed cell death [R].
In people with cancer, treatments that increase Per1 production could decrease tumor growth [R].
Conditions with Increased Gene Activity
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Conditions with Decreased Gene Activity
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Widely expressed. Expressed in hair follicles (at protein level).Found in heart, brain, placenta, lung, liver, skeletal muscle, pancreas, kidney, spleen, thymus, prostate, testis, ovary and small intestine. Highest level in skeletal muscle.
Induction:
Serum-induced levels in fibroblasts show circadian oscillations. Maximum levels after 1 hour stimulation, minimum levels after 12 hours. Another peak is then observed after 20 hours. Protein levels show maximum levels at 6 hours, decrease to reach minimum levels at 20 hours, and increase again to reach a second peak after 26 hours. Levels then decrease slightly and then increase to maximum levels at 32 hours. Levels of phosphorylated form increase between 3 hours and 12 hours.
Molecular Function:
- Chromatin Dna Binding
- E-Box Binding
- Kinase Binding
- Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Dna Binding
- Transcription Factor Activity, Transcription Factor Binding
- Ubiquitin Protein Ligase Binding
Biological Processes:
- Circadian Regulation Of Gene Expression
- Circadian Regulation Of Translation
- Circadian Rhythm
- Entrainment Of Circadian Clock
- Entrainment Of Circadian Clock By Photoperiod
- Histone H3 Acetylation
- Histone H3 Deacetylation
- Histone H4 Acetylation
- Negative Regulation Of Glucocorticoid Receptor Signaling Pathway
- Negative Regulation Of I-Kappab Kinase/Nf-Kappab Signaling
- Negative Regulation Of Jnk Cascade
- Negative Regulation Of Transcription, Dna-Templated
- Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Posttranscriptional Regulation Of Gene Expression
- Regulation Of Circadian Rhythm
- Regulation Of Cytokine Production Involved In Inflammatory Response
- Regulation Of Hair Cycle
- Regulation Of P38mapk Cascade
- Regulation Of Sodium Ion Transport
- Response To Camp
- Transcription, Dna-Templated