Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-9001
Authors: | Scheuren, Maurice Möhner, Jonas Zischler, Hans |
Title: | R-loop landscape in mature human sperm : regulatory and evolutionary implications |
Online publication date: | 18-Apr-2023 |
Year of first publication: | 2023 |
Language: | english |
Abstract: | R-loops are three-stranded nucleic acid structures consisting of an RNA:DNA hybrid and a displaced DNA strand. While R-loops pose a potential threat to genome integrity, they constitute 5% of the human genome. The role of R-loops in transcriptional regulation, DNA replication, and chromatin signature is becoming increasingly clear. R-loops are associated with various histone modifications, suggesting that they may modulate chromatin accessibility. To potentially harness transcription-coupled repair mechanisms in the germline, nearly the entire genome is expressed during the early stages of male gametogenesis in mammals, providing ample opportunity for the formation of a transcriptome-dependent R-loop landscape in male germ cells. In this study, our data demonstrated the presence of R-loops in fully mature human and bonobo sperm heads and their partial correspondence to transcribed regions and chromatin structure, which is massively reorganized from mainly histone to mainly protamine-packed chromatin in mature sperm. The sperm R-loop landscape resembles characteristic patterns of somatic cells. Surprisingly, we detected R-loops in both residual histone and protamine-packed chromatin and localize them to still-active retroposons, ALUs and SINE-VNTR-ALUs (SVAs), the latter has recently arisen in hominoid primates. We detected both evolutionarily conserved and species-specific localizations. Comparing our DNA-RNA immunoprecipitation (DRIP) data with published DNA methylation and histone chromatin immunoprecipitation (ChIP) data, we hypothesize that R-loops epigenetically reduce methylation of SVAs. Strikingly, we observe a strong influence of R-loops on the transcriptomes of zygotes from early developmental stages before zygotic genome activation. Overall, these findings suggest that chromatin accessibility influenced by R-loops may represent a system of inherited gene regulation. |
DDC: | 570 Biowissenschaften 570 Life sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 10 Biologie |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-9001 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
Document type specification: | Scientific article |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Frontiers in genetics 14 |
Pages or article number: | 1069871 |
Publisher: | Frontiers Media |
Publisher place: | Lausanne |
Issue date: | 2023 |
ISSN: | 1664-8021 |
Publisher DOI: | 10.3389/fgene.2023.1069871 |
Appears in collections: | DFG-491381577-G |
Files in This Item:
File | Description | Size | Format | ||
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rloop_landscape_in_mature_hum-20230417112653370.pdf | 2.27 MB | Adobe PDF | View/Open |