希斯甲基转移酶Ezh2通过调节关键再生通路来协调哺乳动物轴突再生
Xue-Wei Wang1,2, Shu-Guang Yang1, Ming-Wen Hu3
1Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
The Journal of clinical investigation
|November 28, 2023
概括
增强Zeste同源2 (Ezh2) 通过调节基因表达,促进哺乳动物中枢神经系统 (CNS) 中的轴突再生. 这一发现为治疗神经退行性疾病和神经损伤提供了新的策略.
科学领域:
- 神经科学是一个神经科学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 在成熟的哺乳动物中枢神经系统 (CNS) 中,神经元再生能力下降,阻碍了受伤和疾病的恢复.
- 目前神经退行性疾病和神经损伤的治疗方法受到中枢神经系统成熟神经元再生不良的限制.
研究的目的:
- 为了研究Ezh2 (增强Zeste同位素2) 在调节哺乳动物轴突再生中的作用.
- 探索Ezh2影响神经元修复和再生的机制.
主要方法:
- 在发育和成年小鼠神经系统中检查了Ezh2表达水平.
- 研究了Ezh2对背部根性质神经元和视网膜质细胞的轴突再生的影响.
- 利用基因操纵 (过度表达) 和分子分析来了解Ezh2的下游目标和机制.
主要成果:
- 在神经系统成熟过程中,Ezh2的表达减少,但在外围神经受伤后,成年后的背根质神经元中增加,促进再生.
- 中枢神经系统视网膜质细胞中Ezh2的过度表达通过表观遗传和非表观遗传途径增强了视神经的再生.
- Ezh2抑制抑制再生的基因,并激活促再生因素,包括下游调节GABA转运体2 (Slc6a13).
结论:
- Ezh2在促进哺乳动物中枢神经系统中轴突再生方面发挥着至关重要的作用.
- 通过Ezh2调节染色质可访问性,为增强中枢神经系统修复提供了一个有希望的治疗策略.
相关概念视频
Spreading of Chromatin Modifications
8.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.3K
Chromatin Modification in iPS Cells
1.7K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K
Histone Modification
13.3K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.3K
Epigenetic Regulation
31.1K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
31.1K
Neurogenesis and Regeneration of Nervous Tissue
826
In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
826
Methods of Nuclear Reprogramming
1.8K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.8K


