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Comprehensive analysis of histone post-translational modifications in mouse and human male germ cells
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 %...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915177/ https://www.ncbi.nlm.nih.gov/pubmed/27330565 http://dx.doi.org/10.1186/s13072-016-0072-6 |
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author | Luense, Lacey J. Wang, Xiaoshi Schon, Samantha B. Weller, Angela H. Lin Shiao, Enrique Bryant, Jessica M. Bartolomei, Marisa S. Coutifaris, Christos Garcia, Benjamin A. Berger, Shelley L. |
author_facet | Luense, Lacey J. Wang, Xiaoshi Schon, Samantha B. Weller, Angela H. Lin Shiao, Enrique Bryant, Jessica M. Bartolomei, Marisa S. Coutifaris, Christos Garcia, Benjamin A. Berger, Shelley L. |
author_sort | Luense, Lacey J. |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0072-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4915177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-49151772016-06-22 Comprehensive analysis of histone post-translational modifications in mouse and human male germ cells Luense, Lacey J. Wang, Xiaoshi Schon, Samantha B. Weller, Angela H. Lin Shiao, Enrique Bryant, Jessica M. Bartolomei, Marisa S. Coutifaris, Christos Garcia, Benjamin A. Berger, Shelley L. Epigenetics Chromatin Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0072-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-06-21 /pmc/articles/PMC4915177/ /pubmed/27330565 http://dx.doi.org/10.1186/s13072-016-0072-6 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Luense, Lacey J. Wang, Xiaoshi Schon, Samantha B. Weller, Angela H. Lin Shiao, Enrique Bryant, Jessica M. Bartolomei, Marisa S. Coutifaris, Christos Garcia, Benjamin A. Berger, Shelley L. Comprehensive analysis of histone post-translational modifications in mouse and human male germ cells |
title | Comprehensive analysis of histone post-translational modifications in mouse and human male germ cells |
title_full | Comprehensive analysis of histone post-translational modifications in mouse and human male germ cells |
title_fullStr | Comprehensive analysis of histone post-translational modifications in mouse and human male germ cells |
title_full_unstemmed | Comprehensive analysis of histone post-translational modifications in mouse and human male germ cells |
title_short | Comprehensive analysis of histone post-translational modifications in mouse and human male germ cells |
title_sort | comprehensive analysis of histone post-translational modifications in mouse and human male germ cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915177/ https://www.ncbi.nlm.nih.gov/pubmed/27330565 http://dx.doi.org/10.1186/s13072-016-0072-6 |
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