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

Abstract

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.

Dexmedetomidine prevents cardiomyocytes from hypoxia/reoxygenation injury via modulating tetmethylcytosine dioxygenase 1-mediated DNA demethylation of Sirtuin1

“…Caffeic acid o-nitro phenethyl ester (CAPE-oNO2) attenuates H/R damage on cardiomyocytes by up-regulating Sirt1 and inactivating NF-κB [ 54 ]. Other studies have illustrated that a slight increase in local DNA methylation hinders Sirt1 expression in white muscles [ 55 ]. In this study, we noticed that DEX facilitated Sirt1 expression, and inhibition of Sirt1 weakened the myocardial protective effect mediated by DEX.…”

Integrated Analyses of DNA Methylation and Gene Expression of Rainbow Trout Muscle under Variable Ploidy and Muscle Atrophy Conditions

“…In gilthead sea bream, and although at a low level, DNA methylation was correlated with expression of the sirtuin-1 gene, a master regulator of metabolism. However, the involvement of other mechanisms in transcriptional regulation was suggested in the study [ 59 ].…”

Understanding how high stocking densities and concurrent limited oxygen availability drive social cohesion and adaptive features in regulatory growth, antioxidant defense and lipid metabolism in farmed gilthead sea bream (Sparus aurata)

“…In any case, most adaptive hypoxia responses appear to be tissue-specific ( Martos-Sitcha et al, 2019a ), and in the absence of transcriptional changes in markers of oxidative metabolism, the skeletal muscle of HD fish disclosed a pronounced upregulation of sirt1 and sirt2 ( Table 4 ). Such metabolic feature is viewed as a higher energy demanding condition that is susceptible to be epigenetically regulated in the case of sirt1 by changes in the DNA methylation pattern of several CpG positions of a CG island close to the transcription start site ( Simó-Mirabet et al, 2020 ). Indeed, it is well known that fasting upregulated the expression of sirt1 in the skeletal muscle of gilthead sea bream ( Simó-Mirabet et al, 2017 ).…”