DNA methylation Landscape of body size variation in sheep.

Jiaxue Cao,Hongping Zhang,Yongfei Du,Zhiyuan Xie,Terence D Capellini,Linjie Wang,Caihong Wei,Jian Lu,Dongming Liu,Shifang Zhang,Huihua Wang,Lixin Du,Tao Zhong,Ruizao Liu,Fuping Zhao,Li Zhang,Mingming Wu,Li Li

doi:10.1038/srep13950

Abstract

Sub-populations of Chinese Mongolian sheep exhibit significant variance in body mass. In the present study, we sequenced the whole genome DNA methylation in these breeds to detect whether DNA methylation plays a role in determining the body mass of sheep by Methylated DNA immunoprecipitation – sequencing method. A high quality methylation map of Chinese Mongolian sheep was obtained in this study. We identified 399 different methylated regions located in 93 human orthologs, which were previously reported as body size related genes in human genome-wide association studies. We tested three regions in LTBP1, and DNA methylation of two CpG sites showed significant correlation with its RNA expression. Additionally, a particular set of differentially methylated windows enriched in the “development process” (GO: 0032502) was identified as potential candidates for association with body mass variation. Next, we validated small part of these windows in 5 genes; DNA methylation of SMAD1, TSC1 and AKT1 showed significant difference across breeds, and six CpG were significantly correlated with RNA expression. Interestingly, two CpG sites showed significant correlation with TSC1 protein expression. This study provides a thorough understanding of body size variation in sheep from an epigenetic perspective.

Highlights

Relates to transgenerational inheritance[13,14,15]
We explored genes within the “Development process” category and considered them as candidate genes related to variation in body mass (Additional Table 6), these genes include Bone morphogenetic protein receptor type-1B (BMPR1B), SMAD1, SMURF1, AKT1 and Tuberous sclerosis 1 (TSC1)
We found that six CpG sites in five regions were significantly correlated with their RNA expression levels (p < 0.05, Fig. 7). 5CpG of Region 4 was negatively correlated with BMPR1B expression, while 1CpG of Region 5 was positively correlated with BMPR1B. 6CpG of Region 9 were negatively correlated with TSC1, whereas 1CpG and 15CpG of Region 10 and 6CpG of Region 7 were positively correlated with AKT1 and SMAD1 expression

Summary

Introduction

Relates to transgenerational inheritance[13,14,15]. DNA methylation reprograms in each generation, and it is possible for it to participate in phenotype divergence and transmit through multiple generations. Chinese Mongolian sheep produces high quality meat with the ability to adapt and survive in a variety of climatic and grazing conditions As a result, this sheep is popularly raised various regions in China including Inner Mongolia (Ujumqin sheep, UQ), Ningxia (Tan sheep, Tan), Shandong (Small-tailed-Han sheep, StH) and Jiangsu provinces (Hu sheep, Hu) (Fig. 1a). We randomly selected two female sheep each from UQ, Tan, StH and Hu, along with two male sheep from UQ in order to detect DNA variation by Methylated DNA immunoprecipitation – sequencing (MeDIP – seq). These studies investigate whether the extent of genome-wide DNA methylation is related to differences in body mass of these four sheep breeds

Methods

Results

Conclusion