Abstract

Female pubertal development is tightly controlled by complex mechanisms, including neuroendocrine and epigenetic regulatory pathways. Specific gene expression patterns can be influenced by DNA methylation changes in the hypothalamus, which can in turn regulate timing of puberty onset. In order to understand the relationship between DNA methylation changes and gene expression patterns in the hypothalamus of pubertal goats, whole-genome bisulfite sequencing and RNA-sequencing analyses were carried out. There was a decline in DNA methylation levels in the hypothalamus during puberty and 268 differentially methylated regions (DMR) in the genome, with differential patterns in different gene regions. There were 1049 genes identified with distinct expression patterns. High levels of DNA methylation were detected in promoters, introns and 3′-untranslated regions (UTRs). Levels of methylation decreased gradually from promoters to 5′-UTRs and increased from 5′-UTRs to introns. Methylation density analysis demonstrated that methylation level variation was consistent with the density in the promoter, exon, intron, 5′-UTRs and 3′-UTRs. Analyses of CpG island (CGI) sites showed that the enriched gene contents were gene bodies, intergenic regions and introns, and these CGI sites were hypermethylated. Our study demonstrated that DNA methylation changes may influence gene expression profiles in the hypothalamus of goats during the onset of puberty, which may provide new insights into the mechanisms involved in pubertal onset.

Highlights

  • The hypothalamus-pituitary-gonadal (HPG) axis plays a critical role in the onset of puberty

  • Global DNA methylation analysis of the hypothalamus was performed with 30× genome coverage and >99% conversion efficiency by whole-genome bisulfite sequencing (WGBS)

  • The genome-wide DNA methylation of the goat hypothalamus during the prepubertal and pubertal stages of development was analyzed for the first time

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Summary

Introduction

The hypothalamus-pituitary-gonadal (HPG) axis plays a critical role in the onset of puberty. Gonadotropin-releasing hormone (GnRH) is secreted by neurosecretory neurons located in the hypothalamus in primates and in the preoptic region in rodents. GnRH secretion is inhibited in embryos and infants and later reactivated, with pulsatile secretion before the onset of puberty [1, 2]. DNA Methylation Patterns of Female Pubertal Goats

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