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HT Experiment :

Experiment Id  GSE115437 Name  HDAC1 modulates OGG1-initiated oxidative DNA damage repair, brain aging, and Alzheimer's disease pathology
Experiment Type  RNA-Seq Study Type  WT vs. Mutant
Source  GEO Curation Date  2023-08-14
description  Unrepaired DNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair activity to stave off age-associated functional decline remain obscure. Here, we show that histone deacetylase 1 (HDAC1) modulates DNA repair in the aging brain via targeting OGG1 of the base excision repair pathway. Mice deficient in HDAC1 display age-associated accumulation of DNA damage in the brain and cognitive impairment. HDAC1 interacts with and positively stimulates OGG1, a DNA glycosylase that primarily acts on 8-oxoguanine (8-oxoG), a type of oxidative DNA damage associated with transcriptional repression. Loss of HDAC1 leads to impaired OGG1 activity, 8-oxoG accumulation at the promoters of a subset of genes critical for brain function, and transcriptional repression. Moreover, we observe elevated 8-oxoG lesions along with reduced HDAC1 activity and downregulation of a similar set genes in the 5XFAD mouse model of Alzheimer's disease (AD). Notably, pharmacological activation of HDAC1 confers protection against the deleterious effects of 8-oxoG lesions in the brains of aged wild-type and 5XFAD mice. Our work uncovers an important role for HDAC1 in the repair of 8-oxoG lesions and highlights HDAC1 activation as a novel therapeutic strategy to counter functional decline during brain aging and neurodegeneration. ChIP-Seq and RNA-Seq of mouse hippocampus, and RNA-Seq of GFAP+ nuclei were isolated from mouse cortex
  • variables:
  • anatomical structure,
  • bulk RNA-seq,
  • genotype

1 Publications

Trail: HTExperiment

34 Samples

Trail: HTExperiment