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Chromatin alterations during the epididymal maturation of mouse sperm refine the paternally inherited epigenome

BACKGROUND: Paternal lifestyle choices and male exposure history have a critical influence on the health and fitness of the next generation. Accordingly, defining the processes of germline programming is essential to resolving how the epigenetic memory of paternal experiences transmits to their offs...

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Autores principales: Bedi, Yudhishtar S., Roach, Alexis N., Thomas, Kara N., Mehta, Nicole A., Golding, Michael C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8734183/
https://www.ncbi.nlm.nih.gov/pubmed/34991687
http://dx.doi.org/10.1186/s13072-021-00433-4
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author Bedi, Yudhishtar S.
Roach, Alexis N.
Thomas, Kara N.
Mehta, Nicole A.
Golding, Michael C.
author_facet Bedi, Yudhishtar S.
Roach, Alexis N.
Thomas, Kara N.
Mehta, Nicole A.
Golding, Michael C.
author_sort Bedi, Yudhishtar S.
collection PubMed
description BACKGROUND: Paternal lifestyle choices and male exposure history have a critical influence on the health and fitness of the next generation. Accordingly, defining the processes of germline programming is essential to resolving how the epigenetic memory of paternal experiences transmits to their offspring. Established dogma holds that all facets of chromatin organization and histone posttranslational modification are complete before sperm exits the testes. However, recent clinical and animal studies suggest that patterns of DNA methylation change during epididymal maturation. In this study, we used complementary proteomic and deep-sequencing approaches to test the hypothesis that sperm posttranslational histone modifications change during epididymal transit. RESULTS: Using proteomic analysis to contrast immature spermatozoa and mature sperm isolated from the mouse epididymis, we find progressive changes in multiple histone posttranslational modifications, including H3K4me1, H3K27ac, H3K79me2, H3K64ac, H3K122ac, H4K16ac, H3K9me2, and H4K20me3. Interestingly, some of these changes only occurred on histone variant H3.3, and most involve chromatin modifications associated with gene enhancer activity. In contrast, the bivalent chromatin modifications, H3K4me3, and H3K27me3 remained constant. Using chromatin immunoprecipitation coupled with deep sequencing, we find that changes in histone h3, lysine 27 acetylation (H3K27ac) involve sharpening broad diffuse regions into narrow peaks centered on the promoter regions of genes driving embryonic development. Significantly, many of these regions overlap with broad domains of H3K4me3 in oocytes and ATAC-seq signatures of open chromatin identified in MII oocytes and sperm. In contrast, histone h3, lysine 9 dimethylation (H3K9me2) becomes enriched within the promoters of genes driving meiosis and in the distal enhancer regions of tissue-specific genes sequestered at the nuclear lamina. Maturing sperm contain the histone deacetylase enzymes HDAC1 and HDAC3, suggesting the NuRD complex may drive some of these changes. Finally, using Western blotting, we detected changes in chromatin modifications between caput and caudal sperm isolated from rams (Ovis aries), inferring changes in histone modifications are a shared feature of mammalian epididymal maturation. CONCLUSIONS: These data extend our understanding of germline programming and reveal that, in addition to trafficking noncoding RNAs, changes in histone posttranslational modifications are a core feature of epididymal maturation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13072-021-00433-4.
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spelling pubmed-87341832022-01-07 Chromatin alterations during the epididymal maturation of mouse sperm refine the paternally inherited epigenome Bedi, Yudhishtar S. Roach, Alexis N. Thomas, Kara N. Mehta, Nicole A. Golding, Michael C. Epigenetics Chromatin Research BACKGROUND: Paternal lifestyle choices and male exposure history have a critical influence on the health and fitness of the next generation. Accordingly, defining the processes of germline programming is essential to resolving how the epigenetic memory of paternal experiences transmits to their offspring. Established dogma holds that all facets of chromatin organization and histone posttranslational modification are complete before sperm exits the testes. However, recent clinical and animal studies suggest that patterns of DNA methylation change during epididymal maturation. In this study, we used complementary proteomic and deep-sequencing approaches to test the hypothesis that sperm posttranslational histone modifications change during epididymal transit. RESULTS: Using proteomic analysis to contrast immature spermatozoa and mature sperm isolated from the mouse epididymis, we find progressive changes in multiple histone posttranslational modifications, including H3K4me1, H3K27ac, H3K79me2, H3K64ac, H3K122ac, H4K16ac, H3K9me2, and H4K20me3. Interestingly, some of these changes only occurred on histone variant H3.3, and most involve chromatin modifications associated with gene enhancer activity. In contrast, the bivalent chromatin modifications, H3K4me3, and H3K27me3 remained constant. Using chromatin immunoprecipitation coupled with deep sequencing, we find that changes in histone h3, lysine 27 acetylation (H3K27ac) involve sharpening broad diffuse regions into narrow peaks centered on the promoter regions of genes driving embryonic development. Significantly, many of these regions overlap with broad domains of H3K4me3 in oocytes and ATAC-seq signatures of open chromatin identified in MII oocytes and sperm. In contrast, histone h3, lysine 9 dimethylation (H3K9me2) becomes enriched within the promoters of genes driving meiosis and in the distal enhancer regions of tissue-specific genes sequestered at the nuclear lamina. Maturing sperm contain the histone deacetylase enzymes HDAC1 and HDAC3, suggesting the NuRD complex may drive some of these changes. Finally, using Western blotting, we detected changes in chromatin modifications between caput and caudal sperm isolated from rams (Ovis aries), inferring changes in histone modifications are a shared feature of mammalian epididymal maturation. CONCLUSIONS: These data extend our understanding of germline programming and reveal that, in addition to trafficking noncoding RNAs, changes in histone posttranslational modifications are a core feature of epididymal maturation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13072-021-00433-4. BioMed Central 2022-01-06 /pmc/articles/PMC8734183/ /pubmed/34991687 http://dx.doi.org/10.1186/s13072-021-00433-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Bedi, Yudhishtar S.
Roach, Alexis N.
Thomas, Kara N.
Mehta, Nicole A.
Golding, Michael C.
Chromatin alterations during the epididymal maturation of mouse sperm refine the paternally inherited epigenome
title Chromatin alterations during the epididymal maturation of mouse sperm refine the paternally inherited epigenome
title_full Chromatin alterations during the epididymal maturation of mouse sperm refine the paternally inherited epigenome
title_fullStr Chromatin alterations during the epididymal maturation of mouse sperm refine the paternally inherited epigenome
title_full_unstemmed Chromatin alterations during the epididymal maturation of mouse sperm refine the paternally inherited epigenome
title_short Chromatin alterations during the epididymal maturation of mouse sperm refine the paternally inherited epigenome
title_sort chromatin alterations during the epididymal maturation of mouse sperm refine the paternally inherited epigenome
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8734183/
https://www.ncbi.nlm.nih.gov/pubmed/34991687
http://dx.doi.org/10.1186/s13072-021-00433-4
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