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Cited by 37Epigenetics and DNA MethylationGenomics and Chromatin DynamicsMolecular Biology Techniques and Applications

DNA methylation and histone post-translational modification stability in post-mortem brain tissue

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Jarmasz, Jessica S., Stirton, Hannah, Davie, James R., Del Bigio, Marc R.·2019·Clinical Epigenetics
DOI 10.1186/s13148-018-0596-7PMC PMC6330433
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Abstract

BACKGROUND: Epigenetic (including DNA and histone) modifications occur in a variety of neurological disorders. If epigenetic features of brain autopsy material are to be studied, it is critical to understand the post-mortem stability of the modifications. METHODS: Pig and mouse brain tissue were formalin-fixed and paraffin-embedded, or frozen after post-mortem delays of 0, 24, 48, and 72 h. Epigenetic modifications frequently reported in the literature were studied by DNA agarose gel electrophoresis, DNA methylation enzyme-linked immunosorbent assays, Western blotting, and immunohistochemistry. We constructed a tissue microarray of human neocortex samples with devitalization or death to fixation times ranging from < 60 min to 5 days. RESULTS: In pig and mouse brain tissue, we found that DNA cytosine modifications (5mC, 5hmC, 5fC, and 5caC) were stable for ≥ 72 h post-mortem. Histone methylation was generally stable for ≥ 48 h (H3K9me2/K9me3, H3K27me2, H3K36me3) or ≥ 72 h post-mortem (H3K4me3, H3K27me3). Histone acetylation was generally less stable. The levels of H3K9ac, H3K27ac, H4K5ac, H4K12ac, and H4K16ac declined as early as ≤ 24 h post-mortem, while the levels of H3K14ac did not change at ≥ 48 h. Immunohistochemistry showed that histone acetylation loss occurred primarily in the nuclei of large neurons, while immunoreactivity in glial cell nuclei was relatively unchanged. In the human brain tissue array, immunoreactivity for DNA cytosine modifications and histone methylation was stable, while subtle changes were apparent in histone acetylation at 4 to 5 days post-mortem. CONCLUSION: We conclude that global epigenetic studies on human post-mortem brain tissue are feasible, but great caution is needed for selection of post-mortem delay matched controls if histone acetylation is of interest.

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Authors
Jarmasz, J. S., Stirton, H., Davie, J. R., & Del Bigio, M. R.
Affiliations
University of Manitoba (CA)
ORCID
Venue
Clinical Epigenetics
Publisher
Springer Science and Business Media LLC
Published
2019-01-11
Volume
11
Issue
1
Pages
5-5
ISSN
  • 1868-7075 (ISSN-L)
  • 1868-7083
DOI
10.1186/s13148-018-0596-7
PMC
PMC6330433
OpenAlex
W2915487859
Cited by
37
References
52
Citations by year
2026: 3 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 3
FWCI
1.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Epigenetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Mspace (University of Manitoba) (submittedVersion)
Funders
  • Canadian Institutes of Health Research (TEC—128094)
  • Canada Research Chairs
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
Keywords
DNA methylation, histone modifications, postmortem brain, postmortem delay, epigenetic stability, histone methylation, histone acetylation, 5-methylcytosine, 5-hydroxymethylcytosine, 5-fluorocytosine, H3K9me2, H3K27me3, H3K36me3, H3K4me3, H3K9ac, H3K27ac, H4K16ac, human neocortex, formalin-fixed paraffin-embedded tissue
MeSH terms
Acetylation, Animals, Autopsy, Brain, Female, Histones, Humans, Male, Protein Processing, Post-Translational, Swine, DNA Methylation, Epigenesis, Genetic, Tissue Array Analysis, Mice

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