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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
Sex differences in histone modifications in the neonatal mouse brain
Houng-Wei Tsai1, Patrick A Grant, Emilie F Rissman
1Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, 22908, USA.
Epigenetics
|November 26, 2008
Summary
Testosterone exposure in utero influences histone modifications, impacting sexual differentiation of the brain. Specifically, testosterone masculinizes histone acetylation in female mouse brains, but not methylation.
Area of Science:
- Neuroscience
- Developmental Biology
- Epigenetics
Background:
- Sexual differentiation of the brain involves cellular processes influenced by neonatal testosterone.
- Testosterone and its metabolite estradiol interact with androgen and estrogen receptors, which can engage histone modifying enzymes.
- Histone modifications like acetylation and methylation are crucial for transcriptional regulation during development.
Purpose of the Study:
- To investigate if histone H3 acetylation and methylation underlie sexual differentiation in specific brain regions.
- To determine if neonatal testosterone mediates observed sex differences in histone modifications.
Main Methods:
- Measurement of acetylated (H3K9/14Ac) and trimethylated (H3K9Me3) histone H3 levels in neonatal mouse brains (whole brain, preoptic area + hypothalamus, amygdala, cortex + hippocampus).
- Experimental manipulation involving administration of testosterone to pregnant dams to assess its mediating role.
- Analysis of histone modifications at embryonic day 18, birth, and postnatal day 6.
Main Results:
- Sex differences (males > females) in both H3K9/14Ac and H3K9Me3 were observed in the cortex + hippocampus (CTX/HIP) at multiple developmental time points.
- In utero testosterone exposure did not alter H3K9Me3 levels, which remained sexually dimorphic.
- Testosterone treatment in pregnant dams led to increased H3K9/14Ac in female offspring, reaching levels comparable to males in the CTX/HIP.
Conclusions:
- Histone modifications, specifically acetylation and methylation of H3, are sexually dimorphic in the developing mouse CTX/HIP.
- Testosterone plays a role in the sexual differentiation of neural development by influencing histone acetylation, but not methylation, in a masculinizing manner.
- This study provides the first evidence linking histone modification patterns to neural sexual differentiation.
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