BioProject

The environmental exposures and lifestyle of parents can alter the development of offspring. More...

The environmental exposures and lifestyle of parents can alter the development of offspring. How this environmental information is coded into heritable messages to be transmitted by gametes remains unknown, but epigenetic mechanisms have been implicated. We recently determined that disruption of histone H3 di-methylation at lysine 4 (H3K4me2) in sperm has transgenerational consequences in the development of offspring. However, little is known about when in spermatogenesis histone methylation is established and whether epimutations induced in developing sperm are permanent. We hypothesize that epigenetic modifications to histones established in spermatogonia persist through spermatogenesis and can be transmitted to offspring via the sperm. Our objective was to determine what genomic regions bearing histone H3K4me2 in spermatogonia are also present in sperm. Methods: Using transgenic mice expressing Oct4-GFP, we isolated an enriched spermatogonia population and performed ChIP-seq for H3K4me2. Results: Our analysis revealed that H3K4me2 is located throughout the genome in spermatogonia and particularly at the transcription start site region (TSS) of more than 16,000 genes. Remarkably 44% of H3K4me2 peaks present in spermatogonia are conserved in sperm. The greatest overlap between spermatogonia and sperm occurred at the TSS with 83% similarity. Finally, we assessed the expression level of genes enriched in H3K4me2 in spermatogonia and sperm. We observed that genes with the highest enrichment in H3K4me2 in sperm are expressed at higher levels in spermatogenesis and during development. Conclusion: These findings suggest that if epimutations are induced in spermatogonia they may persist in sperm and influence the health and development of offspring. Overall design: Examination of H3K4me2 in postnatal spermatogonia from GOF/deltaPE-Oct4/GFP mice isolated by FACS. Less...