Epigenetics Chromatin. 2016 Jun 21;9:24. doi: 10.1186/s13072-016-0072-6. eCollection 2016.
Comprehensive analysis of histone post-translational modifications in mouse and human male germ cells.
Epigenetics & chromatin
Lacey J Luense, Xiaoshi Wang, Samantha B Schon, Angela H Weller, Enrique Lin Shiao, Jessica M Bryant, Marisa S Bartolomei, Christos Coutifaris, Benjamin A Garcia, Shelley L Berger
Affiliations
Affiliations
- Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104 USA.
- Epigenetics Program, University of Pennsylvania, Philadelphia, PA 19104 USA.
- Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104 USA.
- Department of Reproductive Endocrinology and Infertility, Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104 USA.
- Biomedical Sciences Graduate Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA.
- Institute Pasteur, 75724 Paris, France.
PMID: 27330565
PMCID: PMC4915177 DOI: 10.1186/s13072-016-0072-6
Abstract
BACKGROUND: During the process of spermatogenesis, male germ cells undergo dramatic chromatin reorganization, whereby most histones are replaced by protamines, as part of the pathway to compact the genome into the small nuclear volume of the sperm head. Remarkably, approximately 90 % (human) to 95 % (mouse) of histones are evicted during the process. An intriguing hypothesis is that post-translational modifications (PTMs) decorating histones play a critical role in epigenetic regulation of spermatogenesis and embryonic development following fertilization. Although a number of specific histone PTMs have been individually studied during spermatogenesis and in mature mouse and human sperm, to date, there is a paucity of comprehensive identification of histone PTMs and their dynamics during this process.
RESULTS: Here we report systematic investigation of sperm histone PTMs and their dynamics during spermatogenesis. We utilized "bottom-up" nanoliquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) to identify histone PTMs and to determine their relative abundance in distinct stages of mouse spermatogenesis (meiotic, round spermatids, elongating/condensing spermatids, and mature sperm) and in human sperm. We detected peptides and histone PTMs from all four canonical histones (H2A, H2B, H3, and H4), the linker histone H1, and multiple histone isoforms of H1, H2A, H2B, and H3 in cells from all stages of mouse spermatogenesis and in mouse sperm. We found strong conservation of histone PTMs for histone H3 and H4 between mouse and human sperm; however, little conservation was observed between H1, H2A, and H2B. Importantly, across eight individual normozoospermic human semen samples, little variation was observed in the relative abundance of nearly all histone PTMs.
CONCLUSION: In summary, we report the first comprehensive and unbiased analysis of histone PTMs at multiple time points during mouse spermatogenesis and in mature mouse and human sperm. Furthermore, our results suggest a largely uniform histone PTM signature in sperm from individual humans.
Keywords: Epigenetics; Fertility; Histone; Male germ cells; Paternal epigenetics; Post-translational modifications; Sperm; Spermiogenesis; Testes
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