Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline

<p dir="ltr">In somatic cells/tissues, methylation of ribosomal DNA (rDNA) increases with age and age‐related pathologies, which has a direct impact on the regulation of nucleolar activity and cellular metabolism. Here, we used bisulfite pyrosequencing and show that methylation of th...

Full description

Saved in:
Bibliographic Details
Main Author: Ramya Potabattula (4401160) (author)
Other Authors: Federica Zacchini (289957) (author), Grazyna Ewa Ptak (18877204) (author), Marcus Dittrich (167737) (author), Tobias Müller (163591) (author), Nady El Hajj (686554) (author), Thomas Hahn (146530) (author), Charis Drummer (18710925) (author), Rüdiger Behr (705041) (author), Andrea Lucas‐Hahn (18877207) (author), Heiner Niemann (196135) (author), Martin Schorsch (686559) (author), Thomas Haaf (342924) (author)
Published: 2020
Subjects:
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1864513512328396800
author Ramya Potabattula (4401160)
author2 Federica Zacchini (289957)
Grazyna Ewa Ptak (18877204)
Marcus Dittrich (167737)
Tobias Müller (163591)
Nady El Hajj (686554)
Thomas Hahn (146530)
Charis Drummer (18710925)
Rüdiger Behr (705041)
Andrea Lucas‐Hahn (18877207)
Heiner Niemann (196135)
Martin Schorsch (686559)
Thomas Haaf (342924)
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author_facet Ramya Potabattula (4401160)
Federica Zacchini (289957)
Grazyna Ewa Ptak (18877204)
Marcus Dittrich (167737)
Tobias Müller (163591)
Nady El Hajj (686554)
Thomas Hahn (146530)
Charis Drummer (18710925)
Rüdiger Behr (705041)
Andrea Lucas‐Hahn (18877207)
Heiner Niemann (196135)
Martin Schorsch (686559)
Thomas Haaf (342924)
author_role author
dc.creator.none.fl_str_mv Ramya Potabattula (4401160)
Federica Zacchini (289957)
Grazyna Ewa Ptak (18877204)
Marcus Dittrich (167737)
Tobias Müller (163591)
Nady El Hajj (686554)
Thomas Hahn (146530)
Charis Drummer (18710925)
Rüdiger Behr (705041)
Andrea Lucas‐Hahn (18877207)
Heiner Niemann (196135)
Martin Schorsch (686559)
Thomas Haaf (342924)
dc.date.none.fl_str_mv 2020-07-01T00:00:00Z
dc.identifier.none.fl_str_mv 10.1111/acel.13181
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Increasing_methylation_of_sperm_rDNA_and_other_repetitive_elements_in_the_aging_male_mammalian_germline/26095081
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Genetics
Biomedical and clinical sciences
Reproductive medicine
embryo developmental potential
epigenetic clock
germline aging
repetitive DNA elements
ribosomal DNA
sperm DNA methylation
dc.title.none.fl_str_mv Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">In somatic cells/tissues, methylation of ribosomal DNA (rDNA) increases with age and age‐related pathologies, which has a direct impact on the regulation of nucleolar activity and cellular metabolism. Here, we used bisulfite pyrosequencing and show that methylation of the rDNA transcription unit including upstream control element (UCE), core promoter, 18S rDNA, and 28S rDNA in human sperm also significantly increases with donor's age. This positive correlation between sperm rDNA methylation and biological age is evolutionarily conserved among mammals with widely different life spans such as humans, marmoset, bovine, and mouse. Similar to the tandemly repeated rDNA, methylation of human α‐satellite and interspersed LINE1 repeats, marmoset α‐satellite, bovine alpha‐ and testis satellite I, mouse minor and major satellite, and LINE1‐T repeats increases in the aging male germline, probably related to their sperm histone packaging. Deep bisulfite sequencing of single rDNA molecules in human sperm revealed that methylation does not only depend on donor's age, but also depend on the region and sequence context (A vs. G alleles). Both average rDNA methylation of all analyzed DNA molecules and the number of fully (>50%) methylated alleles, which are thought to be epigenetically silenced, increase with donor's age. All analyzed CpGs in the sperm rDNA transcription unit show comparable age‐related methylation changes. Unlike other epigenetic aging markers, the rDNA clock appears to operate in similar ways in germline and soma in different mammalian species. We propose that sperm rDNA methylation, directly or indirectly, influences nucleolar formation and developmental potential in the early embryo.</p><h2>Other Information</h2><p dir="ltr">Published in: Aging Cell<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1111/acel.13181" target="_blank">https://dx.doi.org/10.1111/acel.13181</a></p>
eu_rights_str_mv openAccess
id Manara2_99fc8a1d324536ca1de0c101698ca787
identifier_str_mv 10.1111/acel.13181
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/26095081
publishDate 2020
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv CC BY 4.0
spelling Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germlineRamya Potabattula (4401160)Federica Zacchini (289957)Grazyna Ewa Ptak (18877204)Marcus Dittrich (167737)Tobias Müller (163591)Nady El Hajj (686554)Thomas Hahn (146530)Charis Drummer (18710925)Rüdiger Behr (705041)Andrea Lucas‐Hahn (18877207)Heiner Niemann (196135)Martin Schorsch (686559)Thomas Haaf (342924)Biological sciencesGeneticsBiomedical and clinical sciencesReproductive medicineembryo developmental potentialepigenetic clockgermline agingrepetitive DNA elementsribosomal DNAsperm DNA methylation<p dir="ltr">In somatic cells/tissues, methylation of ribosomal DNA (rDNA) increases with age and age‐related pathologies, which has a direct impact on the regulation of nucleolar activity and cellular metabolism. Here, we used bisulfite pyrosequencing and show that methylation of the rDNA transcription unit including upstream control element (UCE), core promoter, 18S rDNA, and 28S rDNA in human sperm also significantly increases with donor's age. This positive correlation between sperm rDNA methylation and biological age is evolutionarily conserved among mammals with widely different life spans such as humans, marmoset, bovine, and mouse. Similar to the tandemly repeated rDNA, methylation of human α‐satellite and interspersed LINE1 repeats, marmoset α‐satellite, bovine alpha‐ and testis satellite I, mouse minor and major satellite, and LINE1‐T repeats increases in the aging male germline, probably related to their sperm histone packaging. Deep bisulfite sequencing of single rDNA molecules in human sperm revealed that methylation does not only depend on donor's age, but also depend on the region and sequence context (A vs. G alleles). Both average rDNA methylation of all analyzed DNA molecules and the number of fully (>50%) methylated alleles, which are thought to be epigenetically silenced, increase with donor's age. All analyzed CpGs in the sperm rDNA transcription unit show comparable age‐related methylation changes. Unlike other epigenetic aging markers, the rDNA clock appears to operate in similar ways in germline and soma in different mammalian species. We propose that sperm rDNA methylation, directly or indirectly, influences nucleolar formation and developmental potential in the early embryo.</p><h2>Other Information</h2><p dir="ltr">Published in: Aging Cell<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1111/acel.13181" target="_blank">https://dx.doi.org/10.1111/acel.13181</a></p>2020-07-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1111/acel.13181https://figshare.com/articles/journal_contribution/Increasing_methylation_of_sperm_rDNA_and_other_repetitive_elements_in_the_aging_male_mammalian_germline/26095081CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/260950812020-07-01T00:00:00Z
spellingShingle Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline
Ramya Potabattula (4401160)
Biological sciences
Genetics
Biomedical and clinical sciences
Reproductive medicine
embryo developmental potential
epigenetic clock
germline aging
repetitive DNA elements
ribosomal DNA
sperm DNA methylation
status_str publishedVersion
title Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline
title_full Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline
title_fullStr Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline
title_full_unstemmed Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline
title_short Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline
title_sort Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline
topic Biological sciences
Genetics
Biomedical and clinical sciences
Reproductive medicine
embryo developmental potential
epigenetic clock
germline aging
repetitive DNA elements
ribosomal DNA
sperm DNA methylation