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Published on: January 26, 2018
Liver histone H3 methylation and acetylation may associate with type 2 diabetes development
Peipei Tu1, Xiaodan Li, Baicheng Ma
1College of Life Sciences, Nankai University, Nankai,, Tianjin, China, tupeipei_2008@163.com.
Abstract:
Type 2 diabetes (T2D) is a complicated systemic disease, and the exact pathogenetic molecular mechanism is unclear. Distinct histone modifications regulate gene expression in certain diseases, but little is known about histone epigenetics in diabetes. In the current study, C57BL/6 J mice were used to build T2D model, then treated with exendin-4 (10 μg/kg). Histone H3K9 and H3K23 acetylation, H3K4 monomethylation and H3K9 dimethylation were explored by Western blotting of liver histone extracts. Real-time polymerase chain reaction (PCR) was used to examine expression levels of diabetes-related genes, while chromatin immunoprecipitation (ChIP) was applied to analyze H3 and H3K9 acetylation, H3K4 monomethylation, and H3K9 dimethylation in the promoter of facilitated glucose transporter member 2 (Glut2) gene. The results showed that liver's total H3K4 monomethylation and H3K9 dimethylation was increased in diabetic mice, which was abrogated with the treatment of exendin-4. In contrast, H3K9 and H3K23 acetylation were reduced in diabetic mice, while exendin-4 only alleviated the reduction of H3K9 acetylation. Our data indicated that the progression of type 2 diabetes mellitus (T2D) is associated with global liver histone H3K9 and H3K23 acetylation, H3K4 monomethylation, and H3K9 dimethylation. Exploiting exact histone modify enzyme inhibitors, which may represent a novel strategy to prevent T2D.
Insights
Histone modifications in the liver are linked to type 2 diabetes (T2D) progression. Exendin-4 treatment altered these epigenetic marks, suggesting potential new strategies for T2D prevention.
Area of Science:
- Epigenetics
- Molecular Biology
- Endocrinology
Background:
- Type 2 diabetes (T2D) pathogenesis involves complex molecular mechanisms.
- Histone modifications, crucial regulators of gene expression, have roles in various diseases, but their specific involvement in diabetes remains largely unexplored.
Purpose of the Study:
- To investigate the association between specific histone modifications in the liver and the development of T2D.
- To evaluate the impact of exendin-4, a T2D treatment, on these histone modifications.
Main Methods:
- A T2D mouse model was established and treated with exendin-4.
- Western blotting was used to analyze histone modifications (H3K9ac, H3K23ac, H3K4me1, H3K9me2) in liver histone extracts.
- Real-time PCR and Chromatin Immunoprecipitation (ChIP) were employed to assess gene expression and histone modifications at the Glut2 promoter.
Main Results:
- Diabetic mice exhibited increased liver H3K4 monomethylation and H3K9 dimethylation, which were normalized by exendin-4.
- H3K9 and H3K23 acetylation levels were decreased in diabetic mice; exendin-4 partially restored H3K9 acetylation.
- Global liver histone modifications, including H3K9/H3K23 acetylation, H3K4 monomethylation, and H3K9 dimethylation, correlated with T2D progression.
Conclusions:
- Liver histone modifications are significantly associated with type 2 diabetes mellitus progression.
- Targeting histone-modifying enzymes could offer novel therapeutic strategies for preventing or treating T2D.
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