Genome-wide DNA methylation analysis of pituitaries during the initiation of puberty in gilts.

Xiaolong Yuan,Jiaqi Li,Zitao Chen,Zhe Zhang,Shuwen Huang,Zhonghui Li,Hao Zhang,Shaopan Ye,Yuyi Zhong,Nathaniel A Hathaway

doi:10.1371/journal.pone.0212630

Abstract

It has been widely recognized that the early or delayed puberty appears to display harmful effects on adult health outcomes. During the timing of puberty, pituitaries responds to the hypothalamus and then introduce the following response of ovaries in hypothalamic-pituitary-gonadal axis. DNA methylation has been recently suggested to regulate the onset of puberty in female mammals. However, to date, the changes of DNA methylation in pituitaries have not been investigated during pubertal transition. In this study, using gilts as the pubertal model, the genome-scale DNA methylation of pituitaries was profiled and compared across Pre-, In- and Post-puberty by using the reduced representation bisulfite sequencing. We found that average methylation levels of each genomic feature in Post- were lower than Pre- and In-pubertal stage in CpG context, but they were higher in In- than that in Pre- and Post-pubertal stage in CpH (where H = A, T, or C) context. The methylation patterns of CpHs were more dynamic than that of CpGs at the location of high CpG content, low CpG content promoter genes, and differently genomic CGIs. Furthermore, the differently genomic CGIs were likely to show in a similar manner in CpG context but display in a stage-specific manner in the CpH context across the Pre-, In- and Post-pubertal stage. Among these pubertal stages, 5 kb upstream regions of the transcription start sites were protected from both CpG and CpH methylation changes. 12.65% of detected CpGs were identified as the differentially methylated CpGs, regarding 4301 genes which were involved in the fundamental functions of pituitaries. 0.35% of detected CpHs were identified as differentially methylated CpHs, regarding 3691 genes which were involved in the biological functions of releasing gonadotropin hormones. These observations and analyses would provide valuable insights into epigenetic mechanism of the initiation of puberty in pituitary level.

Highlights

In female mammals, the initiation of puberty indicates the achievements of adult height, body proportion, and the capacity of reproduction [1, 2]
An increase in the pulsatile release of gonadotropinreleasing hormone from the hypothalamus results in increased luteinizing hormone and follicle-stimulating hormone release from the pituitary [6, 7], and both luteinizing hormone and follicle-stimulating hormone act on the folliculogenesis, oogenesis, and sex steroid production of the gonads [8,9,10]. These observations indicate that the pituitary exhibits a pivotal role during the onset of puberty, which responds to hypothalamus and introduces the following response of ovaries in HPGs axis
CpG islands (CGIs) are frequently identified as the potential promoters [15] and the regulatory element [16] to support the transcription of genes, and the methylation of CGIs is closely interacted with the methylation of genes [17]

Summary

Introduction

The initiation of puberty indicates the achievements of adult height, body proportion, and the capacity of reproduction [1, 2]. An increase in the pulsatile release of gonadotropinreleasing hormone from the hypothalamus results in increased luteinizing hormone and follicle-stimulating hormone release from the pituitary [6, 7], and both luteinizing hormone and follicle-stimulating hormone act on the folliculogenesis, oogenesis, and sex steroid production of the gonads [8,9,10] These observations indicate that the pituitary exhibits a pivotal role during the onset of puberty, which responds to hypothalamus and introduces the following response of ovaries in HPGs axis. The changes and dynamics of genome-wide DNA methylation during the onset of puberty have been described for the hypothalamus of female goats [25, 26] and rats [27], and these studies have provided useful insights into the epigenetic mechanism for the timing of puberty at hypothalamus level for mammals. Few investigations have focused on the dynamics and changes of DNA methylation in pituitaries during the pubertal transition in mammals

Methods

Results

Conclusion