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Updated: Jun 3, 2025
10:09
Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
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Bidirectional histone monoaminylation dynamics regulate neural rhythmicity
Qingfei Zheng1,2, Benjamin H Weekley3, David A Vinson3
1Department of Radiation Oncology, College of Medicine and Center for Cancer Metabolism, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Nature
|January 8, 2025
Summary
Transglutaminase 2 (TG2) modifies histone H3 at Gln5 with various chemical groups, including histaminylation. This epigenetic mark regulates gene expression, circadian rhythms, and behavior in the brain.
Area of Science:
- Epigenetics
- Neuroscience
- Molecular Biology
Background:
- Histone H3 monoaminylations at Gln5 (H3Q5) are crucial epigenetic marks for gene expression in the brain.
- Transglutaminase 2 (TG2) catalyzes serotonylation (H3Q5ser) and dopaminylation (H3Q5dop) of H3Q5, impacting chromatin states.
Purpose of the Study:
- To investigate TG2's role in H3 monoaminylation beyond serotonylation and dopaminylation.
- To explore the function of H3Q5 histaminylation (H3Q5his) in the brain.
- To elucidate the regulatory mechanisms of circadian gene expression and behavior.
Main Methods:
- Biochemical assays to determine TG2's enzymatic activities.
- Chromatin immunoprecipitation to analyze H3Q5 modifications.
- Studies on gene expression, circadian rhythms, and behavior in animal models.
Main Results:
- TG2 also functions as an eraser and exchanger of H3 monoaminylations, including H3Q5his.
- H3Q5his exhibits diurnal rhythmicity in the brain and influences circadian gene expression and behavior.
- H3Q5his antagonizes H3K4 methyltransferase activity by inhibiting WDR5 binding, unlike H3Q5ser.
Conclusions:
- TG2 integrates chemical signals to modulate epigenetic states, impacting neural rhythmicity.
- H3Q5 monoaminylations represent a dynamic epigenetic layer regulated by TG2.
- The interplay between different H3Q5 modifications fine-tunes gene expression and neural functions.
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