The DNA Methylation Pattern of Prepubertal and Pubertal Alpine Goats

Puberty timing is controlled by many genes and the elements coordinating this process have not completely been identified. Hypothalamus is a pivotal organ in the control of sexual maturation. There is evidence that epigenetic modifications, such as DNA methylation, play a key role in the process. The methylome of the hypothalamus of 10 Alpine goats, 5 at a prepubertal stage (93±8 days old) and 5 at their pubertal stage (230±17 days old) was analysed to investigate the differences at the DNA methylation level behind these physiological changes. In order to evaluate differentially methylated regions, Methylated DNA Binding Domain sequencing (MBD-seq) with enrichment of methylated DNA fragments and next generation sequencing (Hiseq2000 Illumina) were performed. An average of 24,13 million of reads (range 18.00 and 30.11 million of reads) were produced per sample and peaks corresponding to hyper-methylated regions were estimated using the software ChIPseeqer. The analysis showed that there was an increase in methylation before puberty.The extent of methylation had a median value (±IQR) of 12.32±10.21 Mbp of the genome for prepubertal goats, compared with 8.18±9.71 Mbp for pubertal goats. Significantly increased methylation was seen on 11 chromosomes in prepubertal goats. Among these, chromosomes 4 and 7 were the most highly significant differentially methylated. In showing that female puberty in goats is associated with amodification of the DNA methylation pattern in the hypothalamus, these results add information on the complex mechanisms that control puberty in mammals.