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Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease
Lee MY, Lee J, Hyeon SJ, Cho H, Hwang YJ, Shin JY, McKee AC, Kowall NW et al.. Aging cell, 2020-05-17
Topic: Brain proteins, microglia and lab models
The pathogenesis of Alzheimer's disease (AD) and the commonest cause of dementia in the elderly remain incompletely understood. Recently, epigenetic modifications have been shown to play a potential role in neurodegeneration, but the specific involvement of epigenetic signatures landscaped by heterochromatin has not been studied in AD. Herein, we discovered that H3K9me3-mediated heterochromatin condensation is elevated in the cortex of sporadic AD postmortem brains. In order to identify which epigenomes are modulated by heterochromatin, we performed H3K9me3-chromatin immunoprecipitation (ChIP)-sequencing and mRNA-sequencing on postmortem brains from normal subjects and AD patients. The integrated analyses of genome-wide ChIP- and mRNA-sequencing data identified epigenomes that were highly occupied by H3K9me3 and inversely correlated with their mRNA expression levels in AD. Biological network analysis further revealed H3K9me3-landscaped epigenomes to be mainly involved in synaptic transmission, neuronal differentiation, and cell motility. Together, our data show that the abnormal heterochromatin remodeling by H3K9me3 leads to down-regulation of synaptic function-related genes, suggesting that the epigenetic alteration by H3K9me3 is associated with the synaptic pathology of sporadic AD.
Key findings
- Biological network analysis further revealed H3K9me3-landscaped epigenomes to be mainly involved in synaptic transmission, neuronal differentiation, and cell motility.
- Together, our data show that the abnormal heterochromatin remodeling by H3K9me3 leads to down-regulation of synaptic function-related genes, suggesting that the epigenetic alteration by H3K9me3 is associated with the synaptic pathology of sporadic AD.
Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Aging cell) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32419307) |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Lee, M. Y., Lee, J., Hyeon, S. J., Cho, H., Hwang, Y. J., Shin, J. Y., et al. (2020). Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease. Aging cell. https://doi.org/10.1111/acel.13153
Vancouver
Lee MY, Lee J, Hyeon SJ, Cho H, Hwang YJ, Shin JY, et al. Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease. Aging cell. 2020. doi:10.1111/acel.13153. PMID: 32419307.
BibTeX
@article{lee2020-32419307,
author = {Lee, M. Y. and Lee, J. and Hyeon, S. J. and Cho, H. and Hwang, Y. J. and Shin, J. Y. and McKee, A. C. and Kowall, N. W. and others},
title = {{Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease}},
journal = {Aging cell},
year = {2020},
doi = {10.1111/acel.13153},
pmid = {32419307},
url = {https://doi.org/10.1111/acel.13153}
}
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