Genome-wide DNA methylation analysis of the porcine hypothalamus-pituitary-ovary axis

Xiao-Long Yuan,Hao Zhang,Ning Gao,Jia-Qi Li,Per Torp Sangild,Zhe Zhang,Bin Li

doi:10.1038/s41598-017-04603-x

Xiao-Long Yuan, Hao Zhang + Show 5 more

Open Access

https://doi.org/10.1038/s41598-017-04603-x

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Abstract

Previous studies have suggested that DNA methylation in both CpG and CpH (where H = C, T or A) contexts plays a critical role in biological functions of different tissues. However, the genome-wide DNA methylation patterns of porcine hypothalamus-pituitary-ovary (HPO) tissues remain virtually unexplored. In this study, methylomes of HPO tissues were profiled to investigate their differences and similarities. We found that HPO methylomes displayed tissue-specific methylation patterns in both CpG and CpH contexts. At gene locations, the methylation and density of CpGs was negatively linked at transcription start sites but positively linked at transcription end sites. The densities of CpGs and CpHs at CpG island (CGI) locations were negatively correlated with their methylation. Moreover, the methylation interactions between CGIs and genes showed similar pattern in the CpG context but tissue-specific pattern in the CpH context. CpGs located in CGIs, upstream regions and exons were protected from methylation dynamics, whereas CGI shores, CGI shelves and intergenic regions were more likely to be targets of methylation changes. The methylation dynamics enriching in a tissue-specific manner appeared to maintain and establish the biological functions of HPO tissues. Our analyses provided valuable insights into the tissue-specific methylomes of porcine HPO tissues.

Highlights

DNA methylation is one of the best understood epigenetic regulatory mechanisms[1]
CpG island (CGI) that are located at gene promoters are protected from methylation dynamics and exhibit consistently low hypomethylation, which is closely associated with the active transcription[11, 22]
CGIs within gene bodies are frequently susceptible to methylation dynamics and display tissue-specific hypermethylation[21, 23], which is associated with higher gene expression in somatic tissues[24, 25], with the exception of the brain[18, 26]

Summary

Introduction

DNA methylation is one of the best understood epigenetic regulatory mechanisms[1]. There has recently been rapid development of biotechnology for the detection of DNA methylation, and genome-wide DNA methylation pattern profiles have been described for a number of species[2,3,4], tissues[5] and cell types[6], even at a single-cell resolution[7]. CpH methylation has been reported to be negatively correlated with gene activity in the brain genomes of humans[15], mice[17] and birds (great tits)[18, 19] These findings suggest that both CpG and CpH methylation play an important role during the mammalian development and morphogenesis. Pigs and humans share similar genome and physiological characteristics, and previous studies have demonstrated that porcine genome-wide DNA methylation patterns are similar to those observed in humans This finding supports the notion that pigs are a useful and stable biomedical model[12, 27]. Few investigations have focused on the genome-wide DNA methylation profile of the porcine HPO axis

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