Acute irradiation induces a senescence-like chromatin structure in mammalian oocytes
Abstract The mechanisms leading to changes in mesoscale chromatin organization during cellular aging are unknown. Here, we used transcriptional activator-like effectors, RNA-seq and superresolution analysis to determine the effects of genotoxic stress on oocyte chromatin structure. Major satellites...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05641-0 |
| _version_ | 1797388125370056704 |
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| author | Claudia Baumann Xiangyu Zhang Muthugapatti K. Kandasamy Xiaohan Mei Shiyou Chen Kayvan F. Tehrani Luke J. Mortensen Wendy Watford Ashley Lall Rabindranath De La Fuente |
| author_facet | Claudia Baumann Xiangyu Zhang Muthugapatti K. Kandasamy Xiaohan Mei Shiyou Chen Kayvan F. Tehrani Luke J. Mortensen Wendy Watford Ashley Lall Rabindranath De La Fuente |
| author_sort | Claudia Baumann |
| collection | DOAJ |
| description | Abstract The mechanisms leading to changes in mesoscale chromatin organization during cellular aging are unknown. Here, we used transcriptional activator-like effectors, RNA-seq and superresolution analysis to determine the effects of genotoxic stress on oocyte chromatin structure. Major satellites are organized into tightly packed globular structures that coalesce into chromocenters and dynamically associate with the nucleolus. Acute irradiation significantly enhanced chromocenter mobility in transcriptionally inactive oocytes. In transcriptionally active oocytes, irradiation induced a striking unfolding of satellite chromatin fibers and enhanced the expression of transcripts required for protection from oxidative stress (Fermt1, Smg1), recovery from DNA damage (Tlk2, Rad54l) and regulation of heterochromatin assembly (Zfp296, Ski-oncogene). Non-irradiated, senescent oocytes exhibit not only high chromocenter mobility and satellite distension but also a high frequency of extra chromosomal satellite DNA. Notably, analysis of biological aging using an oocyte-specific RNA clock revealed cellular communication, posttranslational protein modifications, chromatin and histone dynamics as the top cellular processes that are dysregulated in both senescent and irradiated oocytes. Our results indicate that unfolding of heterochromatin fibers following acute genotoxic stress or cellular aging induced the formation of distended satellites and that abnormal chromatin structure together with increased chromocenter mobility leads to chromosome instability in senescent oocytes. |
| first_indexed | 2024-03-08T22:36:19Z |
| format | Article |
| id | doaj.art-49ca4c86ce464ed3952593c62a21d619 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-08T22:36:19Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-49ca4c86ce464ed3952593c62a21d6192023-12-17T12:27:18ZengNature PortfolioCommunications Biology2399-36422023-12-016111610.1038/s42003-023-05641-0Acute irradiation induces a senescence-like chromatin structure in mammalian oocytesClaudia Baumann0Xiangyu Zhang1Muthugapatti K. Kandasamy2Xiaohan Mei3Shiyou Chen4Kayvan F. Tehrani5Luke J. Mortensen6Wendy Watford7Ashley Lall8Rabindranath De La Fuente9Department of Physiology and Pharmacology, College of Veterinary Medicine, University of GeorgiaDepartment of Physiology and Pharmacology, College of Veterinary Medicine, University of GeorgiaDepartment of Genetics University of GeorgiaDepartment of Physiology and Pharmacology, College of Veterinary Medicine, University of GeorgiaDepartment of Physiology and Pharmacology, College of Veterinary Medicine, University of GeorgiaRegenerative Biosciences Center (RBC), University of GeorgiaRegenerative Biosciences Center (RBC), University of GeorgiaDepartment of Infectious Diseases, University of GeorgiaDepartment of Physiology and Pharmacology, College of Veterinary Medicine, University of GeorgiaDepartment of Physiology and Pharmacology, College of Veterinary Medicine, University of GeorgiaAbstract The mechanisms leading to changes in mesoscale chromatin organization during cellular aging are unknown. Here, we used transcriptional activator-like effectors, RNA-seq and superresolution analysis to determine the effects of genotoxic stress on oocyte chromatin structure. Major satellites are organized into tightly packed globular structures that coalesce into chromocenters and dynamically associate with the nucleolus. Acute irradiation significantly enhanced chromocenter mobility in transcriptionally inactive oocytes. In transcriptionally active oocytes, irradiation induced a striking unfolding of satellite chromatin fibers and enhanced the expression of transcripts required for protection from oxidative stress (Fermt1, Smg1), recovery from DNA damage (Tlk2, Rad54l) and regulation of heterochromatin assembly (Zfp296, Ski-oncogene). Non-irradiated, senescent oocytes exhibit not only high chromocenter mobility and satellite distension but also a high frequency of extra chromosomal satellite DNA. Notably, analysis of biological aging using an oocyte-specific RNA clock revealed cellular communication, posttranslational protein modifications, chromatin and histone dynamics as the top cellular processes that are dysregulated in both senescent and irradiated oocytes. Our results indicate that unfolding of heterochromatin fibers following acute genotoxic stress or cellular aging induced the formation of distended satellites and that abnormal chromatin structure together with increased chromocenter mobility leads to chromosome instability in senescent oocytes.https://doi.org/10.1038/s42003-023-05641-0 |
| spellingShingle | Claudia Baumann Xiangyu Zhang Muthugapatti K. Kandasamy Xiaohan Mei Shiyou Chen Kayvan F. Tehrani Luke J. Mortensen Wendy Watford Ashley Lall Rabindranath De La Fuente Acute irradiation induces a senescence-like chromatin structure in mammalian oocytes Communications Biology |
| title | Acute irradiation induces a senescence-like chromatin structure in mammalian oocytes |
| title_full | Acute irradiation induces a senescence-like chromatin structure in mammalian oocytes |
| title_fullStr | Acute irradiation induces a senescence-like chromatin structure in mammalian oocytes |
| title_full_unstemmed | Acute irradiation induces a senescence-like chromatin structure in mammalian oocytes |
| title_short | Acute irradiation induces a senescence-like chromatin structure in mammalian oocytes |
| title_sort | acute irradiation induces a senescence like chromatin structure in mammalian oocytes |
| url | https://doi.org/10.1038/s42003-023-05641-0 |
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