ArticleAlzheimer's research & therapy2020
Characterization of the chromatin accessibility in an Alzheimer's disease (AD) mouse model.
Article in Alzheimer's research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 57 citations in OpenAlex.
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- Direct Sequencing of 5-Methylcytosine and 5-Hydroxymethylcytosine at Single-Base Resolution Unravels Their Distinct Roles in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Comparison of the amyloid plaque proteome in Down syndrome, early-onset Alzheimer's disease, and late-onset Alzheimer's disease.Acta neuropathologica · 2025Article
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- Multi-omics insights into the pathogenesis of diabetic cardiomyopathy: epigenetic and metabolic profiles.Epigenomics · 2025Article
- Gaining insights into Alzheimer's disease by predicting chromatin spatial organization.Bioinformatics advances · 2025Article
- Protein swarm-based cause-effect analysis: effects of microRNAs on cooperation networks linking COVID-19 infections, atherosclerosis, and Alzheimer's disease.Frontiers in cardiovascular medicine · 2025Article
- Mechanism of action of "cistanche deserticola-Polygala" in treating Alzheimer's disease based on network pharmacology methods and molecular docking analysis.IET systems biology · 2024Article
- Polygenic risk for alcohol use disorder affects cellular responses to ethanol exposure in a human microglial cell model.Science advances · 2024Article
- Myeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease.Aging cell · 2024Article
- Comparison of the Amyloid Plaque Proteome in Down Syndrome, Early-Onset Alzheimer's Disease and Late-Onset Alzheimer's Disease.Research square · 2024Article
- Gene networks and systems biology in Alzheimer's disease: Insights from multi-omics approaches.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Recognizing Alzheimer's disease from perspective of oligodendrocytes: Phenomena or pathogenesis?CNS neuroscience & therapeutics · 2024Review
- scCASE: accurate and interpretable enhancement for single-cell chromatin accessibility sequencing data.Nature communications · 2024Article
- Ancestry-related differences in chromatin accessibility and gene expression of APOE ε4 are associated with Alzheimer's disease risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Profiling the immune epigenome across global cattle breeds.Genome biology · 2023Article
- A Polyaminobiaryl-Based β-secretase Modulator Alleviates Cognitive Impairments, Amyloid Load, Astrogliosis, and Neuroinflammation in APPInternational journal of molecular sciences · 2023Article
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7 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe pathological hallmarks of Alzheimer's disease (AD) involve alterations in the expression of numerous genes associated with transcriptional levels, which are determined by chromatin accessibility. Here, the landscape of chromatin accessibility was studied to understand the outline of the transcription and expression of AD-associated metabolism genes in an AD mouse model.
methodsThe assay for transposase-accessible chromatin by sequencing (ATAC-seq) was used to investigate the AD-associated chromatin reshaping in the APPswe/PS1dE9 (APP/PS1) mouse model. ATAC-seq data in the hippocampus of 8-month-old APP/PS1 mice were generated, and the relationship between chromatin accessibility and gene expression was analyzed in combination with RNA sequencing. Gene ontology (GO) analysis was applied to elucidate biological processes and signaling pathways altered in APP/PS1 mice. Critical transcription factors were identified; alterations in chromatin accessibility were further confirmed using chromatin immunoprecipitation assays.
resultsWe identified 1690 increased AD-associated chromatin-accessible regions in the hippocampal tissues of APP/PS1 mice. These regions were enriched in genes related to diverse signaling pathways, including the PI3K-Akt, Hippo, TGF-β, and Jak-Stat signaling pathways, which play essential roles in regulating cell proliferation, apoptosis, and inflammatory responses. A total of 1003 decreased chromatin-accessible regions were considered to be related with declined AD-associated biological processes including cellular response to hyperoxia and insulin stimulus, synaptic transmission, and positive regulation of autophagy. In the APP/PS1 hippocampus, 1090 genes were found to be upregulated and 1081 downregulated. Interestingly, enhanced ATAC-seq signal was found in approximately 740 genes, with 43 exhibiting upregulated mRNA levels. Several genes involved in AD development were found to have a significantly increased expression in APP/PS1 mice compared to controls, including Sele, Clec7a, Cst7, and Ccr6. The signatures of numerous transcription factors, including Olig2, NeuroD1, TCF4, and NeuroG2, were found enriched in the AD-associated accessible chromatin regions. The transcription-activating marks of H3K4me3 and H3K27ac were also found increased in the promoters of these genes. These results indicate that the mechanism for the upregulation of genes could be attributed to the enrichment of open chromatin regions with transcription factors motifs and the histone marks H3K4me3 and H3K27ac.
conclusionOur study reveals that alterations in chromatin accessibility may be an initial mechanism in AD pathogenesis.
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