DNA glycosylases Ogg1 and Mutyh influence gene expression of PRC2 targets associated with cognition
Abstract Base excision repair, initiated by DNA glycosylases, preserves genomic integrity by removing damaged bases. DNA glycosylases Ogg1 and Mutyh were shown to alter the hippocampal transcriptome independently of DNA damage repair. However, the role of DNA glycosylases as transcriptional regulato...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-08-01
|
| Series: | Cellular and Molecular Life Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s00018-025-05730-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849237728595542016 |
|---|---|
| author | Andreas Abentung Teri Sakshaug Rabina Dumaru Nina-Beate Liabakk Mingyi Yang Junbai Wang Magnar Bjørås Katja Scheffler |
| author_facet | Andreas Abentung Teri Sakshaug Rabina Dumaru Nina-Beate Liabakk Mingyi Yang Junbai Wang Magnar Bjørås Katja Scheffler |
| author_sort | Andreas Abentung |
| collection | DOAJ |
| description | Abstract Base excision repair, initiated by DNA glycosylases, preserves genomic integrity by removing damaged bases. DNA glycosylases Ogg1 and Mutyh were shown to alter the hippocampal transcriptome independently of DNA damage repair. However, the role of DNA glycosylases as transcriptional regulators and their involvement in cognition remain unclear. Here, we combine transcriptomic and epigenomic analyses of the hippocampus in mice deficient in DNA glycosylases. We report that the combined deficiency of Ogg1 and Mutyh impairs spatial long-term memory. Mechanistically, Ogg1 and Mutyh modulate DNA methylation of polycomb repressive complex 2 (PRC2) target genes. PRC2 occupancy and associated histone post-translational modifications depend on Ogg1 and Mutyh in neurons and glia. These epigenetic changes correlate with cell-type specific differences in gene expression of PRC2 targets. Finally, human genetic data link DNA glycosylase-regulated genes to cognitive function, highlighting a novel role for Ogg1 and Mutyh in modulating the epigenome to control transcriptional responses relevant for brain-related diseases. Graphical Abstract Created in BioRender. Scheffler, K. (2025). https://BioRender.com/jwscej4 . |
| format | Article |
| id | doaj-art-e89a613ba6504d22a1e174721dbcae2a |
| institution | Kabale University |
| issn | 1420-9071 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Springer |
| record_format | Article |
| series | Cellular and Molecular Life Sciences |
| spelling | doaj-art-e89a613ba6504d22a1e174721dbcae2a2025-08-20T04:01:52ZengSpringerCellular and Molecular Life Sciences1420-90712025-08-0182112210.1007/s00018-025-05730-9DNA glycosylases Ogg1 and Mutyh influence gene expression of PRC2 targets associated with cognitionAndreas Abentung0Teri Sakshaug1Rabina Dumaru2Nina-Beate Liabakk3Mingyi Yang4Junbai Wang5Magnar Bjørås6Katja Scheffler7Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)Department of Microbiology, Oslo University Hospital HF, Rikshospitalet and University of OsloDepartment of Clinical Molecular Biology (EpiGen), University of Oslo and Akershus University HospitalDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)Abstract Base excision repair, initiated by DNA glycosylases, preserves genomic integrity by removing damaged bases. DNA glycosylases Ogg1 and Mutyh were shown to alter the hippocampal transcriptome independently of DNA damage repair. However, the role of DNA glycosylases as transcriptional regulators and their involvement in cognition remain unclear. Here, we combine transcriptomic and epigenomic analyses of the hippocampus in mice deficient in DNA glycosylases. We report that the combined deficiency of Ogg1 and Mutyh impairs spatial long-term memory. Mechanistically, Ogg1 and Mutyh modulate DNA methylation of polycomb repressive complex 2 (PRC2) target genes. PRC2 occupancy and associated histone post-translational modifications depend on Ogg1 and Mutyh in neurons and glia. These epigenetic changes correlate with cell-type specific differences in gene expression of PRC2 targets. Finally, human genetic data link DNA glycosylase-regulated genes to cognitive function, highlighting a novel role for Ogg1 and Mutyh in modulating the epigenome to control transcriptional responses relevant for brain-related diseases. Graphical Abstract Created in BioRender. Scheffler, K. (2025). https://BioRender.com/jwscej4 .https://doi.org/10.1007/s00018-025-05730-9DNA glycosylasePRC2EpigenomeTranscriptionCognition |
| spellingShingle | Andreas Abentung Teri Sakshaug Rabina Dumaru Nina-Beate Liabakk Mingyi Yang Junbai Wang Magnar Bjørås Katja Scheffler DNA glycosylases Ogg1 and Mutyh influence gene expression of PRC2 targets associated with cognition Cellular and Molecular Life Sciences DNA glycosylase PRC2 Epigenome Transcription Cognition |
| title | DNA glycosylases Ogg1 and Mutyh influence gene expression of PRC2 targets associated with cognition |
| title_full | DNA glycosylases Ogg1 and Mutyh influence gene expression of PRC2 targets associated with cognition |
| title_fullStr | DNA glycosylases Ogg1 and Mutyh influence gene expression of PRC2 targets associated with cognition |
| title_full_unstemmed | DNA glycosylases Ogg1 and Mutyh influence gene expression of PRC2 targets associated with cognition |
| title_short | DNA glycosylases Ogg1 and Mutyh influence gene expression of PRC2 targets associated with cognition |
| title_sort | dna glycosylases ogg1 and mutyh influence gene expression of prc2 targets associated with cognition |
| topic | DNA glycosylase PRC2 Epigenome Transcription Cognition |
| url | https://doi.org/10.1007/s00018-025-05730-9 |
| work_keys_str_mv | AT andreasabentung dnaglycosylasesogg1andmutyhinfluencegeneexpressionofprc2targetsassociatedwithcognition AT terisakshaug dnaglycosylasesogg1andmutyhinfluencegeneexpressionofprc2targetsassociatedwithcognition AT rabinadumaru dnaglycosylasesogg1andmutyhinfluencegeneexpressionofprc2targetsassociatedwithcognition AT ninabeateliabakk dnaglycosylasesogg1andmutyhinfluencegeneexpressionofprc2targetsassociatedwithcognition AT mingyiyang dnaglycosylasesogg1andmutyhinfluencegeneexpressionofprc2targetsassociatedwithcognition AT junbaiwang dnaglycosylasesogg1andmutyhinfluencegeneexpressionofprc2targetsassociatedwithcognition AT magnarbjøras dnaglycosylasesogg1andmutyhinfluencegeneexpressionofprc2targetsassociatedwithcognition AT katjascheffler dnaglycosylasesogg1andmutyhinfluencegeneexpressionofprc2targetsassociatedwithcognition |