Polymorphism in the PER3 Promoter Associates with Diurnal Preference and Delayed Sleep Phase Disorder

Archer, Simon N.; Carpen, Jayshan D.; Gibson, Mark; Lim, Gim Hui; Johnston, Jonathan D.; Skene, Debra J.; Schantz, Malcolm von

doi:10.1093/sleep/33.5.695

Cited by 126 publications

(87 citation statements)

References 45 publications

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“…The authors propose that SP1 acts with BMAL1 to coregulate circadian gene expression. We have previously shown that the promoter region of human PER3 contains two SP1 sites adjacent to two tandem noncanonical E-box motifs and that a variable number tandemrepeat polymorphism in the PER3 promoter removes one of these SP1 sites and is associated with differences in the levels of reporter gene expression (37). Thus, these data are consistent with a role for SP1 in the regulation of circadian gene expression.…”

Section: Transcripts and Associated Molecular Processes Affected By Dsupporting

confidence: 71%

Mistimed sleep disrupts circadian regulation of the human transcriptome

Archer

Laing

Möller-Levet

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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333

317

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Circadian organization of the mammalian transcriptome is achieved by rhythmic recruitment of key modifiers of chromatin structure and transcriptional and translational processes. These rhythmic processes, together with posttranslational modification, constitute circadian oscillators in the brain and peripheral tissues, which drive rhythms in physiology and behavior, including the sleep-wake cycle. In humans, sleep is normally timed to occur during the biological night, when body temperature is low and melatonin is synthesized. Desynchrony of sleep-wake timing and other circadian rhythms, such as occurs in shift work and jet lag, is associated with disruption of rhythmicity in physiology and endocrinology. However, to what extent mistimed sleep affects the molecular regulators of circadian rhythmicity remains to be established. Here, we show that mistimed sleep leads to a reduction of rhythmic transcripts in the human blood transcriptome from 6.4% at baseline to 1.0% during forced desynchrony of sleep and centrally driven circadian rhythms. Transcripts affected are key regulators of gene expression, including those associated with chromatin modification (methylases and acetylases), transcription (RNA polymerase II), translation (ribosomal proteins, initiation, and elongation factors), temperature-regulated transcription (cold inducible RNA-binding proteins), and core clock genes including CLOCK and ARNTL (BMAL1). We also estimated the separate contribution of sleep and circadian rhythmicity and found that the sleep-wake cycle coordinates the timing of transcription and translation in particular. The data show that mistimed sleep affects molecular processes at the core of circadian rhythm generation and imply that appropriate timing of sleep contributes significantly to the overall temporal organization of the human transcriptome.bloodomics | chronobiology | microarray | genomics | biological rhythms T wenty-four-hour rhythms in physiology and behavior are generated through interaction between environmental cycles and endogenous self-sustained circadian oscillators (1). In mammals, circadian oscillators are present in the brain and most peripheral tissues (2). Circadian rhythmicity within cells in these tissues is generated by a molecular oscillator, which is composed of core transcriptional-translational feedback loops that can also interact with metabolic oscillators (3).The circadian regulation of the mammalian transcriptome includes circadian transcriptional and translational regulation by proteins such as the positive transcription factors CLOCK and ARNTL (BMAL1), and the repressors PERIOD (PER) and CRYPTOCHROME (CRY) (4), chromatin modification by factors such as E1A binding protein P300 (EP300) and the methyltransferase MLL3 (4-6), RNA polymerase activity (4, 7), and posttranscriptional events such as the regulation of ribosome biogenesis and translation (8, 9). Furthermore, physiological factors such as body temperature (10) and endocrine rhythms such as cortisol (11) can modify and reinforce these regulat...

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Section: Transcripts and Associated Molecular Processes Affected By Dsupporting

confidence: 71%

Mistimed sleep disrupts circadian regulation of the human transcriptome

Archer

Laing

Möller-Levet

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

333

317

View full text Add to dashboard Cite

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“…In addition, melatonin – which is often suppressed in night workers – exhibits direct and indirect oncostatic properties specific to colorectal cancer; for example, melatonin can cause growth inhibition of cell lines derived from colon carcinomas in vitro and animal studies 17–19 . Short sleep duration (a common consequence of night shift work) and a length polymorphism in the PER3 clock gene (a genotype associated with morning chronotype and sleep disorders) have been associated with a higher risk for formation of colorectal adenoma, the precursor lesion to colorectal cancer 20, 21 . However, in a recent report, we found no evidence for an association between night shift work and risk for colorectal adenomas among female nurses 22 .…”

Section: Introductionmentioning

confidence: 99%

Rotating night shift work and colorectal cancer risk in the nurses’ health studies

Papantoniou

Devore

Massa

et al. 2018

Intl Journal of Cancer

111

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Animal and human data have suggested that shift work involving circadian disruption may be carcinogenic for humans, but epidemiological evidence for colorectal cancer is still limited. We investigated the association of rotating night shift work and colorectal cancer risk in two prospective female cohorts, the Nurses´ Health Study (NHS) and NHS2, with 24 years of follow up. In total, 190,810 women (NHS=77,439; NHS2=113,371) were included in this analysis, and 1,965 incident colorectal cancer cases (NHS=1,527; NHS2=438) were reported during follow up (NHS: 1988–2012, NHS2: 1989–2013). We used Cox proportional hazards models adjusted for a wide range of potential confounders. We did not observe an association between rotating night work duration and colorectal cancer risk in these cohorts (NHS: 1–14 years: Hazard Ratio (HR) 1.04, 95% CI 0.94, 1.16; 15+ years: HR 1.15, 95% CI 0.95, 1.39; Ptrend=0.14 and NHS2: 1–14 years: HR 0.81, 95% CI 0.66, 0.99; 15+ years: HR 0.96, 95% CI 0.56, 1.64 and Ptrend=0.88). In subsite analysis in NHS, rectal cancer risk increased after long-term (15+ years) rotating night shift work (proximal colon cancer: HR 1.00, 95%CI 0.75, 1.34, Ptrend= 0.90; distal colon cancer: HR 1.27, 95%CI 0.87, 1.85, Ptrend= 0.32; rectal cancer: HR 1.60, 95%CI 1.09, 2.34, Ptrend= 0.02). We found no overall evidence of an association between rotating night shift work and colorectal cancer risk in these two large cohorts of nurses. Risk for rectal cancer significantly increased with shift work duration, suggesting that long-term circadian disruption may play a role in rectal cancer development.

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“…Although knowledge of Per3's role as a component of time-keeping system in humans is limited, a number of reports indicate that hPer3 can be involved in the functioning of sleep [8,24,25] and of certain metabolic processes [11,26]. Per3 alleles seem to influence sleep homeostasis and sleep/wake timing in individuals [8,9] and a strong correlation has been found between the amount of sleep time and Per3 protein secretion in individuals [27].…”

Section: Discussionmentioning

confidence: 99%

“…Per3 alleles seem to influence sleep homeostasis and sleep/wake timing in individuals [8,9] and a strong correlation has been found between the amount of sleep time and Per3 protein secretion in individuals [27]. Compared to four repeat individuals, five repeat individuals tend to experience a greater sense of sleep pressure and, further, tend to demonstrate a poorer cognitive performance when they are sleep deprived.…”

Section: Discussionmentioning

confidence: 99%

“…Per3 consists of 21 exons of which the exon 18 contains a polymorphic repeat domain, with four (Per 3 4 ) or five (Per3 5 ) copies of a tandem repeat region with a length of 54 bp sequence encoding 18 amino acids [5]. Several studies have reported associations of hPer3 alleles with a number of physiopathological conditions, including preference of timing in sleep/wake cycles [6,7], delayed sleep phase syndrome (DSPS) [5][6][7][8], and sleep homeostasis [9]. In Per3 mutant mice, circadian period and phase underwent changes in liver and other peripheral tissues [10].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Per3 length polymorphism in patients with type 2 diabetes mellitus

Ramanujam

Marimuthu

Sooriyakumar

et al. 2013

Hormone Molecular Biology and Clinical Investigation

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Background: A number of observations support the involvement of circadian clock genes in the regulation of metabolic processes. One of these circadian genes, Per3, exhibits a variable number tandem repeat length polymorphism, consisting of two alleles, namely four and five repeat alleles, in its exon 18. The objective of this study was to examine the existence of Per3 variants in patients with type 2 diabetes mellitus (T2DM) as compared to a non T2DM control group. Methods: Intravenous blood samples were collected to obtain white blood cells from 302 T2DM patients and 330 non-diabetic, age-and sex-matched, individuals. Per3 genotyping was performed on DNA by polymerase chain reaction. Results: Frequency of five repeat allele was higher, and that of four repeat allele lower, in T2DM patients as compared to non-diabetic controls (χ 2 = 6.977, p = 0.0082) Conclusions:The results indicate an association of Per3 five repeat allele with T2DM occurrence and suggest that individuals with five repeat allele may be at a greater risk for T2DM as compared to those carrying the four repeat allele.

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Polymorphism in the PER3 Promoter Associates with Diurnal Preference and Delayed Sleep Phase Disorder

Abstract: Polymorphisms in the PER3 promoter could affect its expression, leading to potential differences in the observed functions of PER3.

Cited by 126 publications

References 45 publications

Mistimed sleep disrupts circadian regulation of the human transcriptome

Mistimed sleep disrupts circadian regulation of the human transcriptome

Rotating night shift work and colorectal cancer risk in the nurses’ health studies

Per3 length polymorphism in patients with type 2 diabetes mellitus

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