Promoter methylation analysis of seven clock genes in Parkinson's disease

Lin, Qingling; Ding, Hui; Zhang, Zheng; Gu, Zhuqin; Ma, Jinghong; Chen, Ling; Chan, Piu; Cai, Yanning

doi:10.1016/j.neulet.2011.12.007

Cited by 70 publications

(53 citation statements)

References 22 publications

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“…Parkinson (Lin et al, 2012), whereas DNA hypermethylation-associated loss of BMAL1, which has been reported in leukemia/lymphoma cells, prevents the recruitment of its natural partner, CLOCK, to their common targets, further enhancing the perturbed circadian rhythm of the cancer cells (Taniguchi et al, 2009). Very importantly, a maternal diet rich in fat modulates in utero the acetylation of fetal histone H3 at lysine 14 (H3K14ac) in NPAS2, a paralog of the CLOCK transcription factor, affecting thus the peripheral circadian system of the fetus .…”

Section: Circadian Rhythms and Sleepmentioning

confidence: 99%

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Milagro

Mansego

Miguel

et al. 2013

Molecular Aspects of Medicine

257

161

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Nutritional factors play a life-long role in human health. Indeed, there is growing evidence that one of the mechanisms by which nutrients and bioactive compounds affect metabolic traits is epigenetics. Complex interactions among food components and histone modifications, DNA methylation, non-coding RNA expression and chromatin remodeling factors lead to a dynamic regulation of gene expression that controls the cellular phenotype. Although perinatal period is the time of highest phenotypic plasticity, contributing largely to developmental programming, also during adulthood there is evidence about a nutritional influence on epigenetic regulation. Similarly to type 2 diabetes, hypertension, atherosclerosis and other metabolic disorders, obesity predisposition and weight loss outcomes have been repeatedly associated to changes in epigenetic patterns. Different non-nutritional risk factors that usually accompany obesity seem also to be involved in these epigenetic modifications, especially hyperglycemia, inflammation, hypoxia and oxidative stress. There are currently three major objectives in epigenetic research in relation to obesity: to search for epigenetic biomarkers to predict future health problems or detect the individuals at most risk, to understand the obesity-related environmental factors that could modulate gene expression by affecting epigenetic mechanisms, and to study novel therapeutic strategies based on nutritional or pharmacological agents that can modify epigenetic marks. At this level, the major tasks are: development of robust epigenetic biomarkers of weight regulation, description of those epigenetic marks more susceptible to be modified by dietary exposures, identification of the active ingredients (and the doses) that alter the epigenome, assessment of the real importance of other obesity-related factors on epigenetic regulation, determination of the period of life in which best results are obtained, and understanding of the importance of the inheritance of these epigenetic marks.

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Section: Circadian Rhythms and Sleepmentioning

confidence: 99%

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Milagro

Mansego

Miguel

et al. 2013

Molecular Aspects of Medicine

257

161

View full text Add to dashboard Cite

show abstract

“…[28][29][30] The NPAS2 gene promoter specifically is hypomethylated in Parkinson's disease patients, leading to the suggestion that altered promoter methylation may contribute to abnormal expression of clock genes in this disease. 31 We suggest a possible correlation between promoter regulation and NPAS2 deregulation in melanoma, although this postulate requires further investigation. In particular, nine GGC genotype was more prevalent in melanoma patients in comparison with controls then the other combinations which might correlate with decreased gene expression in 9/9 genotype patients.…”

Section: Discussionmentioning

confidence: 82%

A polymorphic GGC repeat in the NPAS2 gene and its association with melanoma

Franzoni

Markova-Car

Pavlić

et al. 2017

Exp Biol Med (Maywood)

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This report describes a variable microsatellite repeat sequence located in the 5 0 untranslated exon of NSPAS2, a gene encoding a clock transcription factor. Significantly, this study is the first to show that a variant copy number GGC repeat sequence in the NPAS2 clock gene associates with melanoma risk and which may be useful in the assessment of melanoma predisposition. AbstractCircadian clock regulation in mammals is controlled by feedback loops of a set of circadian genes. One of these circadian genes, NPAS2, encodes for a member of the bHLH-PAS class of transcription factors and is expressed in the forebrain and in some peripheral organs such as liver and skin. Other biological processes are also regulated by circadian genes. For example, NPAS2 is involved in cell proliferation, DNA damage repair and malignant transformation. Aberrant expression of clock genes has been previously observed in melanoma which led to our effort to sequence the NPAS2 promoter region in this cancer type. The NPAS2 putative promoter and 5 0 untranslated region of ninety-three melanoma patients and ninety-six control subjects were sequenced and several variants were identified. Among these is a novel microsatellite comprising a GGC repeat with different alleles ranging from 7 to 13 repeats located in the 5 0 untranslated exon. Homozygosity of an allele with nine repeats (9/9) was more prevalent in melanoma than in control subjects (22.6% and 13.5%, respectively, P: 0.0206) suggesting that some NPAS2 variants might contribute to melanoma susceptibility.

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“…As we know, histone acetylation, DNA methylation, non-coding RNA, and so on, play an important role in regulating the expression of clock genes, and ultimately, circadian phenotypes [93]. Abnormal CpG methylation has been observed in neurodegenerative disorders, including PD [94][95][96]. In PD, the methylation status in the NPAS2 (the paralog of Clock) promoter is decreased and the NPAS2 expression is increased.…”

Section: Clock Gene Differencementioning

confidence: 99%

“…This, in turn, would activate the expression of Rora and Rev-erba, which serve as the main regulators of Bmal1 expression. Above all, the epigenetic alterations in NPSA2 expression may be the primary cause of changes in Bmal1 and Bmal2 in the leukocytes of PD patients [96]. Curtis AM et al identified the importance of Bmal1 in modulating the inflammatory response, by regulating miR-155 and some proinflammatory cytokines including TNF-a [97].…”

Section: Clock Gene Differencementioning

confidence: 99%

A New Perspective for Parkinson’s Disease: Circadian Rhythm

Wang

et al. 2016

Neurosci. Bull.

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Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson's disease (PD) exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative consequences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.

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Promoter methylation analysis of seven clock genes in Parkinson's disease

Cited by 70 publications

References 22 publications

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

A polymorphic GGC repeat in the NPAS2 gene and its association with melanoma

A New Perspective for Parkinson’s Disease: Circadian Rhythm

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