Puberty is the gateway to adult reproductive competence, encompassing a suite of complex, integrative, and coordinated changes in neuroendocrine functions. However, the regulatory mechanisms of transcriptional reprogramming in the arcuate nucleus (
ARC) during onset of puberty are still not fully understood. To understand the role of epigenetics in regulating gene expression, mouse hypothalamic
ARCs were isolated at 4 and 8 weeks, and the transcriptome,
DNA hydroxymethylation, DNA methylation, and
chromatin accessibility were assessed via
RNA sequencing (
RNA-seq), reduced representation
bisulfite sequencing (RRBS-seq), reduced representation hydroxymethylation profiling (RRHP)-seq, and assay for
transposase-accessible
chromatin (ATAC-seq), respectively. The overall
DNA hydroxymethylation and DNA methylation changes in
retroelements (REs) were associated with gene expression modeling for puberty in the
ARC. We focused on analyzing
DNA hydroxymethylation and DNA methylation at two short interspersed nuclear elements (SINEs) located on the promoter of the
5-hydroxytryptamine receptor 6 (Htr6) gene and the enhancer of the
KISS-1 metastasis suppressor (Kiss1) gene and investigated their regulatory roles in gene expression. Our data uncovered a novel epigenetic mechanism by which SINEs regulate gene expression during puberty.