S-specific methylome patterns. Methylome variation in cisregulatory regions is known to
S-specific methylome patterns. Methylome variation in cisregulatory regions is recognized to affect the binding affinity of methyl-sensitive DNA-binding regulatory factors (including TFs)25,44,67,68. Moreover, methylation-associated alterations in chromatin accessibility might also impede the binding affinity of such components and may be associated with altered TF activity and modifications in transcription20,67. Alternatively, altered TF activity, arising from species-specific mutations inside TF binding sequence motifs or in TF binding domains, has also been reported to generate methylome divergence in cis and trans24, and could also underlie species-specific epigenetic divergence. Our final results suggest a tight hyperlink involving TF activity and methylome divergence, that could participate in reshaping the transcriptional network of your livers in Lake Malawi cichlids. TE and repetitive sequences present on average higher methylation levels than the genome-wide average (Fig. 1d), although some certain TE classes show much more variable and reduce levels (Supplementary Fig. 6d, e). DNA methylation-mediated transcriptional repression of mainly deleterious TE elements is critical to the integrity of most eukaryote genomes, from plants to fish and mammals, and can be mediated in both animals and plants by tiny non-coding RNAs, for instance piwi-interacting RNAs (piRNAs) in zebrafish and mammals18,19,69. Notably, the majority ( 60 ) of species differences in methylation patterns associated with transcriptional adjustments in liver was substantially localised in evolutionary young transposon/repeat regions, notably in intergenic retroposons in the vicinity of genes and in intronic DNA transposons (Dunn’s test p 10-10; Fig. 3c and Supplementary Fig. 10b). Although the majority of TE activity is beneath tight cellular handle to ensure genome stability, transposition events have also been associated with genome evolution and phenotypic diversification. Indeed, TE insertion might represent a source of functional genomic variation and novel cis-regulatory elements, underlying altered transcriptional network45,47,48,70. In haplochromine cichlids, variation in anal fin egg-spots patterns associated with courtship behaviour, has been linked to a novel cis-regulatory element, derived from TE sequences46. In addition, Brawand and colleagues have revealed that most TE insertions close to genes in East African cichlids were associated with altered gene expression patterns38. Furthermore, genes in piRNA-related pathways have been reported to be under optimistic selection in Lake Malawi mTORC1 Activator Storage & Stability cichlid flock, in line using a rapid evolving TE sequence landscape observed in cichlids36, and these genes could also be associated with TE-related methylome variation, equivalent to Arabidopsis11,71. Not just can novel TE insertions participate in genome evolution, DNA methylation at TE-derived cis-regulatory elements has been shown to have an effect on transcriptional activity of nearby genes12,45. In rodents, the insertion of 1 IAP (intra-cisternal ANATURE COMMUNICATIONS | (2021)12:5870 | doi/10.1038/s41467-021-26166-2 | www.nature.com/naturecommunicationsARTICLENATURE COMMUNICATIONS | doi/10.1038/s41467-021-26166-particle) retrotransposon in the upstream cis-regulatory region of the PPARĪ± Antagonist Storage & Stability agouti gene is connected with considerable phenotypic variation of coat colours and metabolic adjustments. Differential methylation levels at this TE-derived ectopic promoter straight impacts the activity on the agouti gene5,28, and such epigenetic patterns of.