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Updated: Mar 18, 2026

Chromatin Extraction from Frozen Chimeric Liver Tissue for Chromatin Immunoprecipitation Analysis
Published on: March 23, 2021
Chromatin variation associated with liver metabolism is mediated by transposable elements
Juan Du1, Amy Leung2, Candi Trac2
1Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, CA USA ; Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA USA.
Transposable elements (TEs), particularly younger long interspersed nuclear elements (LINEs), drive variable chromatin accessibility in mice. This variation influences metabolic gene expression and contributes to phenotypic diversity, especially under dietary stress.
Area of Science:
- Genomics
- Epigenetics
- Systems Biology
Background:
- Chromatin accessibility is crucial for transcriptional regulation and linked to complex traits.
- Significant variation in chromatin accessibility across individuals remains unexplained.
- Understanding the drivers of chromatin variation is key to understanding phenotypic diversity.
Purpose of the Study:
- To investigate the role of transposable elements (TEs) in chromatin accessibility variation.
- To explore how chromatin variation at TEs contributes to phenotypic diversity in response to diet.
- To identify mechanisms influencing chromatin variation at TEs.
Main Methods:
- Profiling chromatin accessibility in liver from seven mouse strains with diverse phenotypes.
- Analyzing the association of variable chromatin sites with transposable elements (TEs).
- Using CRISPR-Cas9 to delete variable chromatin sites and assess effects on gene expression.
Main Results:
- Variable chromatin accessibility sites were enriched at specific TEs, especially younger long interspersed nuclear elements (LINEs).
- Younger LINEs associated with immune factors, older LINEs with liver-specific factors.
- Deletion of TE-associated variable chromatin sites altered nearby metabolic gene expression, linking TE-driven chromatin variation to metabolic regulation.
Conclusions:
- Specific TEs contribute significantly to chromatin accessibility variation across mouse strains.
- Chromatin variation at TEs is a key factor in phenotypic diversity, particularly in response to dietary challenges like high-fat/high-sucrose diets.
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