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Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
Histone H3 is aberrantly phosphorylated in glutamine-repeat diseases
Ikuru Yazawa1, Noriko Hazeki, Hirofumi Nakase
1Department of Neurology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan. ikuru@toranomon.gr.jp
Biochemical and Biophysical Research Communications
|February 21, 2003
Summary
Aberrant phosphorylation of histone H3 is a key finding in glutamine-repeat diseases, impacting neuronal inclusions and nuclei. This suggests a common pathological mechanism across these neurodegenerative conditions.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Glutamine-repeat diseases, such as Huntington's disease, are characterized by protein aggregation in neurons.
- Aberrant protein modification, including phosphorylation, is implicated in neurodegeneration.
Purpose of the Study:
- To investigate aberrant phosphorylation in neuronal inclusions and nuclei in glutamine-repeat diseases.
- To identify the specific protein target of aberrant phosphorylation.
Main Methods:
- Double-labeling immunohistochemistry with anti-ubiquitin and anti-phosphoserine antibodies.
- Enzymatic dephosphorylation techniques.
- Fluorescence-activated cell sorting (FACS) for nuclear inclusion isolation.
- Immunoblotting of aggregated nuclear proteins.
Main Results:
- Neuronal inclusions and nuclei show aberrant phosphorylation in brain tissues from patients with glutamine-repeat diseases.
- Histone H3 was identified as the target protein exhibiting aberrant phosphorylation.
- Increased histone H3 phosphorylation was observed in diseased brains compared to controls.
Conclusions:
- Aberrant phosphorylation of histone H3 is a shared pathological process in glutamine-repeat diseases.
- This finding provides a potential common molecular mechanism contributing to the pathology of these disorders.
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