Remodeling of the Epigenetic Landscape in Rainbow Trout, Oncorhynchus Mykiss, Offspring In Response To Maternal Choline Intake

Authors: FREIJ, KHALID - University Of Alabama; Cleveland, Beth; BIGA, PEGGY - University Of Alabama

Submitted to: Comparative Biochemistry and Physiology, Part D: Genomics and Proteomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/28/2024
Publication Date: 10/31/2024
Citation: Freij, K., Cleveland, B.M., Biga, P. 2024. Remodeling of the Epigenetic Landscape in Rainbow Trout, Oncorhynchus Mykiss, Offspring In Response To Maternal Choline Intake. Comparative Biochemistry and Physiology, Part D: Genomics and Proteomics. 52(2024):101348. https://doi.org/10.1016/j.cbd.2024.101348.
DOI: https://doi.org/10.1016/j.cbd.2024.101348

Interpretive Summary: Maternal nutrient intake during pregnancy or egg development can have lasting effects in offspring, a concept described as "nutritional imprinting". Previously, we determined that differences in dietary choline intake in rainbow trout broodstock changes the gene expression profile of the hatched offspring. However, it remains unknown whether these changes are associated with epigenetic modifications in genes, a methylation mechanism through which gene expression can be regulated. We analyzed the DNA methylome in offspring and found very low correlation between gene methylation levels and transcript abundance, indicating the diet effects on gene expression are not driven primarily by diet-induced changes in DNA methylation. These findings provide insight into mechanisms of nutritional imprinting and contribute to the development of feeding strategies that improve production efficiency through intervention in broodstock nutrition.

Technical Abstract: The objective of this paper was to investigate whether changes in the methylome in rainbow trout (Oncorhynchus mykiss) are associated with transcriptomic responses during early development in response to maternal dietary choline intake. Three experimental diets were formulated to have different levels of choline: (a) 2065 ppm choline (Low Choline, 0% supplementation), (b) 5657 ppm choline (Medium Choline, 0.6% supplementation), and (c) 9248 ppm choline (High Choline, 1.2% choline supplementation). Six rainbow trout families were fed experimental diets beginning 18 months post-hatch until spawning; their offspring were fed a commercial diet. Reduced representational bisulfite sequencing (RRBS) was utilized to measure genome-wide methylation differences in offspring immediately after hatching. When comparing to the Medium Choline offspring, differential DNA methylation occurred more in the Low Choline offspring than High Choline, especially in genic features like promoters. The differentially methylated CpGs (q = 0.01) were identified evenly between CpG islands and shores in the genome, mostly found in the introns of genes. Genes such as Fabp2 and LEAP2B associated with protein binding, fatty acid binding, DNA binding, and response to bacteria were differentially methylated and detected as differentially regulated genes by previous RNA-seq analysis. These findings indicate that levels of dietary choline available in broodstock diets alters offspring DNA methylation; however, most differentially expressed genes were not associated with differential DNA methylation, suggesting additional mechanisms playing a role in regulating gene expression in response to maternal choline intake.