1; Supplementary Fig. 10f), that are important metabolic variables in steroid and
1; Supplementary Fig. 10f), which are vital metabolic factors in steroid and fatty acid metabolism, as well as genes encoding other hepatic enzymes involved in energy balance processes. This enrichment is associated with considerable methylome divergence among species, in distinct in promoter regions and gene bodies (Fig. 3d). As an example, the gene sulfurtransferase tstd1-like, an enzyme involved in energy balance and the mitochondrial metabolism, is expressed exclusively within the liver in the deep-water pelagic species D. limnothrissa, where it shows 80 decreased methylation Traditional Cytotoxic Agents Inhibitor web levels ina gene-body DMR in comparison with all the other species (Fig. 3e, h). An additional example could be the promoter from the enzyme carbonyl reductase [NADPH] 1 (cbr1) which shows important hypomethylation (two.2kbp-long DMR) in the algae-eaters MZ and PG, linked with up to 60-fold enhanced gene expression in their livers compared to the predatory Rhamphochromis and Diplotaxodon (Fig. 3f, i). Interestingly, cbr1 is involved within the metabolism of numerous fatty acids in the liver and has been associated with fatty acid-mediated cellular signalling in response to environmental perturbation51. As a final instance, we highlight the cytotoxic effector perforin 1-like (prf1-like), an essential player in liver-mediated power balance and immune functions52. Its promoter is hypermethylated (88 mCG/CG) exclusively in theNATURE COMMUNICATIONS | (2021)12:5870 | doi/10.1038/s41467-021-26166-2 | www.nature.com/naturecommunicationsNATURE COMMUNICATIONS | doi/10.1038/s41467-021-26166-ARTICLEFig. 3 Methylome divergence is linked with differential transcriptional activity in Lake Malawi cichlids. a Heatmap and unsupervised hierarchical clustering of gene expression values (Z-score) of all differentially expressed genes (DEGs) located amongst livers of four Lake Malawi cichlid species (Wald tests corrected for multiple testing making use of false discovery price FDR 1 ). GO enrichment evaluation for three DEG clusters are shown in Supplementary Fig. 9c. b Significant overlap between DEG and differentially expressed regions (DMRs; p 0.05) linked to a gene (precise hypergeometric test, p = four.71 10-5), highlighting putative functional DMRs (pfDMRs). c Bar plot showing the SIRT6 Activator custom synthesis percentage of pfDMRs localised in either promoters, intergenic regions (0.5-4kbp away from genes), or in gene bodies, with all the proportion of TE content for every single group. d Heatmap representing important GO terms for DEGs related with pfDMRs for each and every genomic function. GO categories: BP, Biological Method; MF, Molecular Function. Only GO terms with Benjamini -Hochberg FDR-corrected p-values 0.05 are shown. Examples of pfDMRs substantially related with species-specific liver transcriptional changes for the genes thiosulfate:glutathione sulfurtransferase tstd1-like (LOC101468457; q = 6.82 10-16) (e), carbonyl reductase [NADPH]-1 cbr1-like (LOC101465189; MZ vs DL, q = 0.002; MZ vs RL, q = 1.18 10-7) (f) and perforin-1 prf1-like (LOC101465185; MZ vs DL, q = three.68 10-19; MZ vs RL, q = 0.00034) (g). Liver and muscle methylome profiles in green and purple, respectively (averaged mCG/CG levels [ ] in 50 bp bins; n = 3 biological replicates for liver DL, PG, and MZ; n = 2 biological replicates for liver RL, AS, and AC, and muscle DL, RL, and PG). h-j Boxplots showing gene expression values (transcript per million) for the genes in (e-g). in livers (green) and muscle (pink). n = three biological replicates for liver DL, MZ, PG; n = two biological.
