DNA methylation of the promoter region of bnip3 and bnip3l genes induced by metabolic programming

Abstract

BackgroundEnvironmental changes of biotic or abiotic nature during critical periods of early development may exert a profound influence on physiological functions later in life. This process, named developmental programming can also be driven through parental nutrition. At molecular level, epigenetic modifications are the most likely candidate for persistent modulation of genes expression in later life.ResultsIn order to investigate epigenetic modifications induced by programming in rainbow trout, we focused on bnip3 and bnip3l paralogous genes known to be sensitive to environmental changes but also regulated by epigenetic modifications. Two specific stimuli were used: (i) early acute hypoxia applied at embryo stage and (ii) broodstock and fry methionine deficient diet, considering methionine as one of the main methyl-group donor needed for DNA methylation. We observed a programming effect of hypoxia with an increase of bnip3a and the four paralogs of bnip3l expression level in fry. In addition, parental methionine nutrition was correlated to bnip3a and bnip3lb1 expression showing evidence for early fry programming. We highlighted that both stimuli modified DNA methylation levels at some specific loci of bnip3a and bnip3lb1.ConclusionOverall, these data demonstrate that methionine level and hypoxia stimulus can be of critical importance in metabolic programming. Both stimuli affected DNA methylation of specific loci, among them, an interesting CpG site have been identified, namely − 884 bp site of bnip3a, and may be positively related with mRNA levels.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5048-4) contains supplementary material, which is available to authorized users.

Early feeding of rainbow trout (Oncorhynchus mykiss) with methionine deficient diet over a two-week period: consequences for liver mitochondria in juveniles

“…As such, methionine potentially represents a critical factor in nutritional programming. In this regard, we recently reported that feeding a methionine-deficient diet to rainbow trout broodstock for 6 months affected the activation and/or expression of several key metabolic factors in offspring through DNA methylation (Veron et al, 2018), confirming the possibility of nutritional programming in fish through parental methionine nutrition (Fontagné-Dicharry et al, 2017;Seiliez et al, 2017).…”

“…This finding is supported by several studies which demonstrated that early imbalanced dietary methionine led to modulation of DNA and histone methylation later in life through the control of the one-carbon metabolism (Rees, 2002;Waterland, 2006;Waterland and Jirtle, 2004). Recently, we also reported that for both broodstock and early fry, methionine nutrition affected the methylation of several CpG sites and the mRNA levels of bnip3a (bcl-2/E1B-19K interacting protein 3) and bnip3lb1 (also known as nix) genes involved in mitochondrial mediated apoptosis and/or mitophagy (Veron et al, 2018). In the present study, we did not observe any modulation of global DNA methylation in the livers of fish from fry fed the MD diet compared with their control counterparts.…”

“…In addition to its role as a building block for protein synthesis, methionine has recently emerged as a key factor in modulating several cell signalling pathways (Belghit et al, 2014;Séité et al, 2018;Skiba-Cassy et al, 2016), the antioxidant defence system (Andersen et al, 2016;Fontagné-Dicharry et al, 2015;Séité et al, 2018;Tesseraud et al, 2009) and the epigenetic processes of histone and DNA methylation (Veron et al, 2018;Waterland, 2006), and (n=6) and were analysed using two-way ANOVA or PERMANOVA, followed by Tukey's post hoc test for multiple comparisons. Where the interaction between diet and nutritional past is significant (asterisks), lowercase letters in the graphs represent statistically significant differences (P<0.05, Tukey's HSD).…”

Stearoyl-CoA desaturase (scd1a) is epigenetically regulated by broodstock nutrition in gilthead sea bream (Sparus aurata)

“…At the same time, more proximal CpG islands in mice showed no variation [45]. This seems not unusual, as studying the possibility to program the response to hypoxia and dietary methionine deficiencies in rainbow trout, it was observed that the methylation level of targeted genes was consistently low (0 to 3%) in proximal positions (until -600 bp), being more susceptible to be methylated the CpG sites at more distal positions [53].…”

“…Different studies in fish have revealed how the early environment can have long lasting-effects on the later phenotype and on the ability to adapt to environmental conditions later in life (reviewed by [50]). Such early stimuli refer, among others, to temperature at larval stage [51], cold-shock and air-exposure to embryos and larvae [52], early acute hypoxia at embryo stage, broodstock or fry methionine deficient diets [53], and first feeding with carbohydrates [54], a mix of plant proteins [55] or soya-based diets [56,57]. There is also experimental evidence for the nutritional programing of lipid metabolism in both fish [20,38,39,40,41,42], and higher vertebrates [48,49], though the epigenetic mechanisms regulating the expression of key genes such as fads2 and scd1 remains elusive in fish, and in marine fish in particular.…”