Abstract
BackgroundSirtuins (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).MethodsGene 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.ResultsThe 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.ConclusionsThe gene organization of SIRTs is highly conserved in vertebrates. GSB sirt family members have CGI- and 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.
Highlights
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
Our results indicate that the summer decrease in sirt1 expression is concurrent with the increased DNA methylation at the sirt1 promoter, which was especially evident in young fish at CpG positions containing SP1 binding sites (CpG2, 3 and CpG12–14, 16)
This study demonstrates that the gene structure of sirts is highly conserved through vertebrate evolution in the fish lineage
Summary
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. Biomarkers that identify and follow up desired traits are especially appropriate for the selection of environmental conditions and genotypes that promote or exhibit better physiological performances [2,3,4] This is of particular relevance for productive traits related to intermediary metabolism that are not easy to measure (e.g., feed efficiency, energy status, redox homeostasis). Gene expression patterns of growth-promoting factors and antioxidant markers or lipid- and energymetabolism-related markers have become highly informative for disclosing different metabolic features in challenged fish and higher vertebrates [5,6,7] In this sense, sirtuins (SIRTs) are a conserved family of enzymes that couple protein deacylation with the energy status of the cell via the cellular NAD+/NADH ratio, linking nutrition and energy status with epigenetic regulation [8,9,10]. In gilthead sea bream (Sparus aurata) (GSB), the patterns of sirt gene expression are powerful biomarkers at the tissue-specific level, as they disclose different energy statuses resulting from nutrient availability or growth potentiality [4, 11, 12]
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