Changes in human sirtuin 6 gene promoter methylation during aging

Sahin, Kaniye; Yılmaz, Sevgi; Gözükırmızı, Nermin

doi:10.3892/br.2014.266

Cited by 14 publications

(8 citation statements)

References 25 publications

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“…CpG sites can regulate the effect of transcription via changing methylation states[31–33]. In the current study, analyses of CGI sites demonstrated that the gene regions whose methylation level changed from prepuberty to puberty were gene bodies, intergenic regions, introns and exons, rather than promoter regions, which is not consistent with previous reports[34]. These CGI sites that were not located in the promoter may exert an important effect on regulating gene expression[35].…”

Section: Discussioncontrasting

confidence: 95%

DNA Methylation Patterns in the Hypothalamus of Female Pubertal Goats

Yang

et al. 2016

PLoS ONE

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Female pubertal development is tightly controlled by complex mechanisms, including neuroendocrine and epigenetic regulatory pathways. Specific gene expression patterns can be influenced by DNA methylation changes in the hypothalamus, which can in turn regulate timing of puberty onset. In order to understand the relationship between DNA methylation changes and gene expression patterns in the hypothalamus of pubertal goats, whole-genome bisulfite sequencing and RNA-sequencing analyses were carried out. There was a decline in DNA methylation levels in the hypothalamus during puberty and 268 differentially methylated regions (DMR) in the genome, with differential patterns in different gene regions. There were 1049 genes identified with distinct expression patterns. High levels of DNA methylation were detected in promoters, introns and 3′-untranslated regions (UTRs). Levels of methylation decreased gradually from promoters to 5′-UTRs and increased from 5′-UTRs to introns. Methylation density analysis demonstrated that methylation level variation was consistent with the density in the promoter, exon, intron, 5′-UTRs and 3′-UTRs. Analyses of CpG island (CGI) sites showed that the enriched gene contents were gene bodies, intergenic regions and introns, and these CGI sites were hypermethylated. Our study demonstrated that DNA methylation changes may influence gene expression profiles in the hypothalamus of goats during the onset of puberty, which may provide new insights into the mechanisms involved in pubertal onset.

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Section: Discussioncontrasting

confidence: 95%

DNA Methylation Patterns in the Hypothalamus of Female Pubertal Goats

Yang

et al. 2016

PLoS ONE

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“…This notion fits well with the early appearance of CGIs during vertebrate evolution and is associated with an increased concentration of CGIs close to TSSs from cold-blooded vertebrates to warm-blooded vertebrates [53]. To the best of our knowledge, this general trend has not been assessed in SIRT genes, but interestingly, the occurrence of CGIs has been reported in SIRT promoters of humans [54][55][56][57][58], mice [59] and ruminants [60][61][62]. In contrast, in GSB, the occurrence of CGIs was only found in sirt1 and sirt3.…”

Section: Cgis In Sirt Promoters Appeared Early During Vertebrate Evolsupporting

confidence: 77%

Local DNA methylation helps to regulate muscle sirtuin 1 gene expression across seasons and advancing age in gilthead sea bream (Sparus aurata)

et al. 2020

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Background: Sirtuins (SIRTs) are master regulators of metabolism, and their expression patterns in gilthead sea bream (GSB) reveal different tissue metabolic capabilities and changes in energy status. Since little is known about their transcriptional regulation, the aim of this work was to study for the first time in fish the effect of age and season on sirt gene expression, correlating expression patterns with local changes in DNA methylation in liver and white skeletal muscle (WSM). Methods: Gene organization of the seven sirts was analyzed by BLAT searches in the IATS-CSIC genomic database (www.nutrigroup-iats.org/seabreamdb/). The presence of CpG islands (CGIs) was mapped by means of MethPrimer software. DNA methylation analyses were performed by bisulfite pyrosequencing. A PCR array was designed for the simultaneous gene expression profiling of sirts and related markers (cs, cpt1a, pgc1α, ucp1, and ucp3) in the liver and WSM of one-and three-year-old fish during winter and summer. Results: The occurrence of CGIs was evidenced in the sirt1 and sirt3 promoters. This latter CGI remained hypomethylated regardless of tissue, age and season. Conversely, DNA methylation of sirt1 at certain CpG positions within the promoter varied with age and season in the WSM. Among them, changes at several SP1 binding sites were negatively correlated with the decrease in sirt1 expression in summer and in younger fish. Changes in sirt1 regulation match well with variations in feed intake and energy metabolism, as judged by the concurrent changes in the analyzed markers. This was supported by discriminant analyses, which identified sirt1 as a highly responsive element to age-and season-mediated changes in energy metabolism in WSM. Conclusions: The gene organization of SIRTs is highly conserved in vertebrates. GSB sirt family members have CGIand non-CGI promoters, and the presence of CGIs at the sirt1 promoter agrees with its ubiquitous expression. Gene expression analyses support that sirts, especially sirt1, are reliable markers of age-and season-dependent changes in energy metabolism. Correlation analyses suggest the involvement of DNA methylation in the regulation of sirt1 expression, but the low methylation levels suggest the contribution of other putative mechanisms in the transcriptional regulation of sirt1.

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“…Age-dependent downregulation of SIRT1 favours acetylation of nuclear factor (NF)-kB p65, leading to its nuclear translocation and transcription of inflammatory genes (Yeung et al 2004). Recent work has shown that sirtuin expression can be modulated by epigenetic changes, namely increased DNA methylation and non-coding RNAs such as miR-200a and miR-34a (Eades et al 2011;Sahin et al 2014;Yu et al 2015). The maintenance of SIRT1 homeostasis is fundamental to repression of detrimental pathways of arterial ageing such as the Forkhead transcription factor (FOXO) pathway (Brunet et al 2004).…”

Section: Sirt1mentioning

confidence: 99%

Ageing, metabolism and cardiovascular disease

Costantino

Paneni

Cosentino

2015

The Journal of Physiology

355

252

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Age is one of the major risk factors associated with cardiovascular disease (CVD). About one‐fifth of the world population will be aged 65 or older by 2030, with an exponential increase in CVD prevalence. It is well established that environmental factors (overnutrition, smoking, pollution, sedentary lifestyles) may lead to premature defects in mitochondrial functionality, insulin signalling, endothelial homeostasis and redox balance, fostering early senescent features. Over the last few years, molecular investigations have unveiled common signalling networks which may link the ageing process with deterioration of cardiovascular homeostasis and metabolic disturbances, namely insulin resistance. These different processes seem to be highly interconnected and their interplay may favour adverse vascular and cardiac phenotypes responsible for myocardial infarction, stroke and heart failure. In the present review, we carefully describe novel molecular cues underpinning ageing, metabolism and CVD. In particular, we describe a dynamic interplay between emerging pathways such as FOXOs, AMPK, SIRT1, p66Shc, JunD and NF‐kB. This overview will provide the background for attractive molecular targets to prevent age‐driven pathology in the vasculature and the heart.

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Changes in human sirtuin 6 gene promoter methylation during aging

Cited by 14 publications

References 25 publications

DNA Methylation Patterns in the Hypothalamus of Female Pubertal Goats

DNA Methylation Patterns in the Hypothalamus of Female Pubertal Goats

Local DNA methylation helps to regulate muscle sirtuin 1 gene expression across seasons and advancing age in gilthead sea bream (Sparus aurata)

Ageing, metabolism and cardiovascular disease

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