Integrative Genome-Wide DNA Methylome and Transcriptome Analysis of Ovaries from Hu Sheep with High and Low Prolific.

Xiaolei Yao,Zongyou Wei,Feng Wang,Xu Feng,Fengzhe Li,Fan Yang,M A Ei-Samahy

doi:10.3389/fcell.2022.820558

Abstract

DNA methylation plays an important role in biological processes by affecting gene expression. However, how DNA methylation regulates phenotypic variation in Hu sheep remains unclear. Therefore, we generated genome-wide DNA methylation and transcriptomic profiles in the ovaries of Hu sheep with different prolificacies and genotypes (FecBB and FecB+). Results showed that ovary DNA methylome and transcriptome were significantly different between high prolificacy and low prolificacy Hu sheep. Comparative methylome analyses identified 10,644, 9,594, and 12,214 differentially methylated regions and 87, 1,121, and 2,375 genes, respectively, showing differential expression levels in three different comparison groups. Female reproduction-associated differentially methylated regions-related genes and differentially expressed genes were enriched, thereby the respective interaction networks were constructed. Furthermore, systematical integrative analyses revealed a negative correlation between DNA methylation around the transcriptional start site and gene expression levels, which was confirmed by testing the expression of integrin β2 subunit (ITGB2) and lysosome-associated protein transmembrane-4 beta (LAPTM4B) in vivo and in vitro. These findings demonstrated that DNA methylation influences the propensity for prolificacy by affecting gene expression in the ovaries, which may contribute to a greater understanding of the epigenome and transcriptome that will be useful for animal breeding.

Highlights

Litter size is one of most important traits that determines the fecundity and reproductive efficiency of sheep bred for meat
To determine the effects of DNA methylation on the phenotypic variation of prolificacy, whole-genome bisulfite sequencing (WGBS) analysis was performed in the ovaries of HPBB, LPBB and LPB + groups of Hu sheep
It has been demonstrated that the homozygous mutation (BB) had the higher fecundity than the heterozygous mutation (B+) or wild-type (++), significant differences in prolificacy phenotypes were found in the same genotype (BB) of Hu sheep with under the same feeding conditions

Summary

Introduction

Litter size is one of most important traits that determines the fecundity and reproductive efficiency of sheep bred for meat. In China, most sheep species are monotocous and seasonal estrus, a few are polytocous. Hu sheep is an excellent local breed in China, which is known for its high prolificacy and year-round estrus (Yue, 1996). Determining the molecular mechanisms associated with fecundity will help accelerate the breeding process of sheep with high prolificacy. The existing genetic studies have identified several genes with sheep fecundity, including GDF9, BMP15, and BMPR1B, the underlying genetic mechanisms remain largely unexplored (Chu et al, 2007; Polley et al, 2010; Farhadi et al, 2013; Wang et al, 2015).

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