PER1

Description

The PER1 (period circadian regulator 1) is a protein-coding gene located on chromosome 17.

Period circadian protein homolog 1 is a protein in humans that is encoded by the PER1 gene.

== Function == The PER1 protein is important to the maintenance of circadian rhythms in cells, and may also play a role in the development of cancer. This gene is a member of the period family of genes. It is expressed with a daily oscillating circadian rhythm, or an oscillation that cycles with a period of approximately 24 hours. PER1 is most notably expressed in the region of the brain called the suprachiasmatic nucleus (SCN), which is the primary circadian pacemaker in the mammalian brain. PER1 is also expressed throughout mammalian peripheral tissues. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. Circadian expression of PER1 in the suprachiasmatic nucleus will free-run in constant darkness, meaning that the 24-hour period of the cycle will persist without the aid of external light cues. Subsequently, a shift in the light/dark cycle evokes a proportional shift of gene expression in the suprachiasmatic nucleus. The time of gene expression is sensitive to light, as light during a mammal's subjective night results in a sudden increase in per expression and thus a shift in phase in the suprachiasmatic nucleus.

PER1, a transcriptional repressor, is a core component of the circadian clock, an internal timekeeping system that regulates various physiological processes. This clock generates approximately 24-hour rhythms in gene expression, influencing metabolism and behavior. It acts as a vital regulator of functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. The circadian clock has two key components: the central clock, located in the suprachiasmatic nucleus (SCN) of the brain, and peripheral clocks present in most tissues and organs. Both clocks can be reset by environmental cues, known as Zeitgebers (German for 'timegivers'). Light, sensed by the retina, is the primary Zeitgeber for the central clock, which directly signals the SCN. The central clock entrains the peripheral clocks via neuronal and hormonal signals, body temperature, and feeding cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow organisms to achieve temporal homeostasis with their environment by regulating gene expression, creating a peak of protein expression every 24 hours to control the activity of physiological processes. The transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1, and CRY2) are essential for rhythm generation. Post-translational modifications (PTMs) play a role in determining the period (tau) of rhythms. A diurnal rhythm synchronizes with the day/night cycle, while ultradian and infradian rhythms have periods shorter and longer than 24 hours, respectively. Disruptions in 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 BMAL1 or BMAL2, form the positive limb of the feedback loop, acting as a heterodimer and activating 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, transcriptional repressors, form the negative limb of the feedback loop, interacting with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer, inhibiting its activity and negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop, activating and repressing BMAL1 transcription, respectively. PER1 regulates circadian target genes' expression at post-transcriptional levels, potentially without being required for repression at the transcriptional level. It controls PER2 protein decay and represses CRY2, preventing its repression on CLOCK/BMAL1 target genes such as FXYD5 and SCNN1A in the kidney and PPARA in the liver. Besides its involvement in the circadian clock, PER1 regulates several processes. It 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 BMAL1:CLOCK. PER1 plays a role in modulating the neuroinflammatory state via the regulation of inflammatory mediators' release, such as CCL2 and IL6. In spinal astrocytes, it negatively regulates the MAPK14/p38 and MAPK8/JNK MAPK cascades and the subsequent activation of NFkappaB. PER1 coordinately regulates the expression of multiple genes involved in regulating renal sodium reabsorption. It can act as a gene expression activator in a gene and tissue-specific manner, enhancing WNK1 and SLC12A3 expression in the kidney in collaboration with CLOCK. PER1 modulates hair follicle cycling and represses the CLOCK-BMAL1-induced transcription of BHLHE40/DEC1.

PER1 is also known as PER, RIGUI, hPER.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing