Abstract

BackgroundCoexpression network analysis is a powerful tool to reveal transcriptional regulatory mechanisms, identify transcription factors, and discover gene functions. It can also be used to investigate changes in coexpression patterns in response to environmental insults or changes in experimental conditions. Maternal nutrition is considered a major intrauterine regulator of fetal developmental programming. The objective of this study was to investigate structural changes in gene coexpression networks in the muscle of bull beef calves gestated under diets with or without methionine supplementation. Both muscle transcriptome and methylome were evaluated using next generation sequencing.ResultsMaternal methionine supplementation significantly perturbed coexpression patterns in the offspring’s muscle. Indeed, we found that neither the connection strength nor the connectivity pattern of six modules (subnetworks) detected in the control diet were preserved in the methionine-rich diet. Functional characterization revealed that some of the unpreserved modules are implicated in myogenesis, adipogenesis, fibrogenesis, canonical Wnt/β-catenin pathway, ribosome structure, rRNA binding and processing, mitochondrial activities, ATP synthesis and NAD(P) H oxidoreductases, among other functions. The bisulfite sequencing analysis showed that nearly 2% of all evaluated cytosines were differentially methylated between maternal diets. Interestingly, there were significant differences in the levels of gene body DNA methylation between preserved and unpreserved modules.ConclusionsOverall, our findings provide evidence that maternal nutrition can significantly alter gene coexpression patterns in the offspring, and some of these perturbations are mediated by changes in DNA methylation.

Highlights

  • Coexpression network analysis is a powerful tool to reveal transcriptional regulatory mechanisms, identify transcription factors, and discover gene functions

  • Overall, our findings provide evidence that maternal nutrition can significantly alter gene coexpression patterns in the offspring, and some of these perturbations are mediated by changes in DNA methylation

  • We evaluated gene coexpression networks in the muscle of bull beef calves gestated under a control or methionine-rich diet, we functionally characterized the subnetworks altered by maternal methionine supplementation, and we investigated the link between network perturbation and DNA methylation

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Summary

Introduction

Coexpression network analysis is a powerful tool to reveal transcriptional regulatory mechanisms, identify transcription factors, and discover gene functions. The objective of this study was to investigate structural changes in gene coexpression networks in the muscle of bull beef calves gestated under diets with or without methionine supplementation Both muscle transcriptome and methylome were evaluated using generation sequencing. It is wellaccepted that genes that are controlled by the same set of transcription factors or are involved in the same biological processes tend to have similar expression profiles [3]. This principle is known as guilt-by-association and represents the basis for the reconstruction of gene networks using RNA sequencing data. These networks, commonly called gene coexpression networks, are undirected graphs where nodes correspond to genes and edges represent pairwise expression similarities

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