The chromatin mapping of H3K4me3 and H3K27me3 modification in ovaries during porcine puberty initiation

Abstract

Background The biological structure and function of mammalian ovaries undergo important developmental changes during pre- puberty. Posttranslational modified histones dynamically regulate ovarian development, which also can respond to the onset of puberty with heritable changes in gene expression that are associated with nucleosome modifications. This research used chromatin immunoprecipitation followed by sequencing (ChIP-seq) technology and bioinformatic analysis to confirm the histone-DNA interaction in pre-puberty ovarian follicles (PreOV) and in-puberty ovarian follicles (InOV). Then, employed qRT-PCR, and cell proliferation and apoptosis testing to further investigate the function of H3K4me3and H3K27me3 in gene transcription and cell growth. Results With the onset of puberty, ChIP-Seq found 946 higher- enrichment and 916 lower- enrichment genes were significantly differentially modified with H3K4me3, while 1954 higher- enrichment and 882 lower- enrichment genes were significantly differentially modified with H3K27me3 in InOV vs. PreOV. Then interestingly, 88 significantly genes were associated with significantly differentially H3K4me3-enriched, H3K4me3-delepted, H3K27me3-enriched, and H3K27me3-delepted modifications, which also were related to female gemmate development pathway, bone mineralization and fatty acid transport, including FOXO3, RUNX1, NOBOX, DMRT1, MYC, LEPTIN, ACVR2, and BMPR1B. Furthermore, compare medium-sized antral with Graff follicles, FOXO3, RUNX1 and BMPR1B were low expressed in medium-sized antral follicles, while NOBOX and LEPTIN were low expressed in Graff follicles. Finally, H3K4me3 exhibited to promote proliferation and anti-apoptosis, whereas H3K27me3 was more to inhibited proliferation and induced cell apoptosis in porcine granulosa cells (pGCs). Conclusions The genome-wide modified profile of H3K4me3 and H3K27me3 showed that H3K27me3 modification was more active than H3K4me3 modification during the onset of puberty in porcine ovaries. H3K4me3 and H3K27me3 acted as activator and repressor to regulate gene transcription that are related to porcine puberty initiation process. Genes including FOXO3, BMPR1B, LEPTIN, RUNX1, involved in networks of female gamete generation pathway associating with ovarian follicle development, ovulation, ovulation cycle process and female gonad development, which showed the further direction to investigate the function of H3K4me3/H3K27me3-targets in puberty initiation.