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Updated: Jun 4, 2026
09:41
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Changed histone acetylation patterns in normal-appearing white matter and early multiple sclerosis lesions
Xiomara Pedre1, Fabrizio Mastronardi, Wolfgang Bruck
1Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.
Summary
Histone acetylation increases in aged and multiple sclerosis (MS) brains, inhibiting oligodendrocyte differentiation. Histone deacetylation occurs early in MS, decreasing with disease duration.
Area of Science:
- Neuroscience
- Epigenetics
- Cell Biology
Background:
- Oligodendrocyte differentiation is regulated by histone modifications, specifically acetylation and deacetylation.
- Histone acetylation, mediated by histone acetyltransferases (HATs) and histone deacetylases, influences gene transcription.
- Previous studies in rodents indicated histone deacetylation promotes oligodendrocyte differentiation, while acetylation inhibits it.
Purpose of the Study:
- To investigate the role of histone modifications in human brain aging and multiple sclerosis (MS).
- To examine changes in histone H3 acetylation and deacetylation in MS lesions.
- To correlate these epigenetic changes with oligodendrocyte differentiation inhibitors and disease progression.
Main Methods:
- Analysis of histone H3 acetylation and deacetylation in human brain samples from aged subjects and MS patients.
- Immunohistochemistry to detect acetylated histone H3 in NogoA+ oligodendrocytes.
- Quantitative PCR to measure transcript levels of HATs and oligodendrocyte differentiation inhibitors.
- Chromatin immunoprecipitation to assess histone H3 acetylation at target gene promoters.
Main Results:
- Increased histone H3 acetylation was observed in the white matter of aged human brains and in chronic MS lesions.
- Elevated levels of acetylated histone H3 were found in oligodendrocytes within a subset of MS samples.
- These acetylation changes correlated with increased expression of oligodendrocyte differentiation inhibitors (TCF7L2, ID2, SOX2) and higher HAT transcript levels (CBP, P300), particularly in female MS patients.
- Chromatin immunoprecipitation confirmed enrichment of acetyl-histone H3 at the promoter of TCF7L2 in MS patient samples.
- In contrast, early MS lesions showed significant oligodendroglial histone deacetylation.
Conclusions:
- Histone acetylation is associated with aging and chronic multiple sclerosis in the human brain.
- The shift towards histone acetylation in chronic MS correlates with increased transcriptional inhibitors, potentially hindering oligodendrocyte differentiation.
- Histone deacetylation appears to be an early event in MS, with its efficacy diminishing as the disease progresses.
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