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DNA glycosylases Ogg1 and Mutyh mediate gene expression of PRC2 targets important for memory formation

ABSTRACT: DNA glycosylases Ogg1 and Mutyh mediate gene expression of PRC2 targets important for memory formation

PROVIDER: PRJNA1137411 | ENA |

REPOSITORIES: ENA

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DNA glycosylases Ogg1 and Mutyh mediate gene expression of PRC2 targets important for memory formation (RNA-Seq)

Project description:Base excision repair initiated by DNA glycosylases is known to preserve genomic integrity by removing damaged bases. Besides, DNA glycosylases Ogg1 and Mutyh were shown to alter the hippocampal transcriptome associated with cognition but independent of DNA damage repair. However, the underlying molecular mechanisms are not fully understood. 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 but not associative long-term memory. Mechanistically, Ogg1 and Mutyh modulate DNA methylation of polycomb repressive complex 2 (PRC2) target genes. We find that the occupancy of PRC2 and histone modifications associated with PRC2 activity depend on Ogg1 and Mutyh in neurons and glia. These epigenetic changes correlate with cell-type specificdifferences in gene expression of PRC2 targets. Our results uncover a novel role for Ogg1 and Mutyh beyond DNA repair in modulating the epigenome to control transcriptional responses in the brain important for memory formation.

2025-08-13 | GSE272602 | GEO

DNA glycosylases Ogg1 and Mutyh mediate gene expression of PRC2 targets important for memory formation (ChIP-Seq)

2025-08-13 | GSE272601 | GEO

DNA glycosylases Ogg1 and Mutyh mediate gene expression of PRC2 targets important for memory formation (BiSulfite-Seq)

2025-08-13 | GSE272600 | GEO

DNA glycosylases Ogg1 and Mutyh mediate gene expression of PRC2 targets important for memory formation (BiSulfite-Seq)

Project description:DNA glycosylases Ogg1 and Mutyh mediate gene expression of PRC2 targets important for memory formation (BiSulfite-Seq)

| PRJNA1137412 | ENA

DNA glycosylases Ogg1 and Mutyh mediate gene expression of PRC2 targets important for memory formation (ChIP-Seq)

Project description:DNA glycosylases Ogg1 and Mutyh mediate gene expression of PRC2 targets important for memory formation (ChIP-Seq)

| PRJNA1137414 | ENA

DNA glycosylases Ogg1 and Mutyh mediate gene expression of PRC2 targets important for memory formation (RNA-Seq)

Project description:DNA glycosylases Ogg1 and Mutyh mediate gene expression of PRC2 targets important for memory formation (RNA-Seq)

| PRJNA1137413 | ENA

DNA-seq of mitochondrial DNA from liver of OGG1 and MUTYH deficient mice that have been bred for five consecutive generations

Project description:Studying whether removal of base-excision repair from mitochondria will result into increase in mitochondrial DNA (mtDNA) mutation load. The endogenous genes of OGG1 and MUTYH DNA glycosylases were modified to lack the genomic region encoding for the predicted mitochondrial targeting sequence. The mouse lines used: A mouse line that lacks the region encoding for the mitochondrial targeting sequence (L2 to W23) of OGG1 (Ogg1 dMTS mice). A mouse line that lacks the region encoding the mitochondrial targeting sequence (K2 to P33) of MUTYH (Mutyh dMTS mice). To accumulate mutations to the mitochondrial DNA these mice were bred double homozygous Mutyh dMTS x Ogg1 dMTS mice as a maternal lineage for five consecutive generations and mitochondrial DNA from liver was extracted from the offspring and sequenced with Illumina. OGG1 and MUTYH are involved in repair of 8-oxo-dG from DNA. 8-oxo-dG can be a mutagenic lesion because some DNA repair polymerases are known to erroneously incorporate adenosine opposite to 8-oxo-dG during replication leading to GC>TA transversion mutations.

2018-07-13 | E-MTAB-6532 | biostudies-arrayexpress

Genome-wide analysis of 6 month old hippocampal gene expression in Ogg1- and/or Mutyh-deficent mice

Project description:Oxidative DNA damage has been associated with cognitive decline. The Ogg1 and Mutyh DNA glycosylases cooperate to prevent mutations caused by 8-oxoG, a major premutagenic oxidative DNA base lesion. Here, we have examined behavior and cognitive function in mice deficient of these glycosylases. We found that Ogg1-/-Mutyh-/- mice were more active and less anxious and that their learning ability was impaired. In contrast, Mutyh-/- mice showed moderately improved memory compared to WT. There was no change in genomic 8-oxoG levels, suggesting that Ogg1 and Mutyh play minor roles in global repair in adult brain. Notably, transcriptome analysis of hippocampus revealed that differentially expressed genes in the mutant mice belong to pathways known to be involved in anxiety and cognitive function. Thus, beyond their involvement in DNA repair, Ogg1 and Mutyh modulate cognitive function and behavior, and related hippocampal gene expression, suggesting a novel role for 8-oxoG in regulating adaptive behavior.

2015-12-20 | GSE73029 | GEO

Genomic 8-oxoguanine modulates gene transcription independent of its repair by DNA glycosylases OGG1 and MUTYH

Project description:It has been suggested that the oxidtaive DNA base lesion 8-oxo-7,8-dihydroguanine (OG) and its repair has epigenetic-like properties and mediates transcription, but genome-wide evidence of this interdependence is lacking. Here, we applied an improved OG-sequencing approach reducing artificial background oxidation and RNA- sequencing to correlate genome-wide distribution of OG with gene transcription in HAP1 cells deficient for OGG1 and/or MUTYH. Our data identified moderate enrichment of OG in the genome that is mainly driven by the genomic context and not affected by DNA glycosylase-initiated repairs. Regardless of DNA glycosylase activity, OG in promoter regions correlated with expression of genes related to metabolic processes and damage response pathways indicating that it functions as a sensor of cellular stress to regulate transcription. Our work provides novel insights into the mechanism underlying transcriptional regulation by OG and DNA glycosylases OGG1 and MUTYH and suggests that oxidative DNA damage accumulation and its repair utilize different pathways.

2024-12-21 | GSE256080 | GEO

Genomic 8-oxoguanine modulates gene transcription independent of its repair by DNA glycosylases OGG1 and MUTYH [RNA-seq]

2024-12-31 | GSE256081 | GEO