甲暴露诱导系统性表观遗传变化 基因组甲基化和乙化
bioRxiv : the preprint server for biology
|March 10, 2025
概括
甲暴露会改变基因组的修饰,这表明其致癌性的表观遗传机制. 这项研究揭示了对甲的新见解.
科学领域:
- 环境健康 环境健康
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 毒理学 毒理学 毒理学
背景情况:
- 甲 (FA) 是已知的人类致癌物质,但仅仅它的基因毒性作用并不能完全解释其致癌潜力.
- 表观遗传机制,特别是基因组转化后修饰 (PTMs),越来越被认为是致癌的关键.
- 基因组PTMs,如甲基化和乙化,调节基因表达,并且可以通过环境暴露而改变.
研究的目的:
- 调查甲暴露对基因素甲基化和乙化模式的影响.
- 探索潜在的表观遗传机制,这是甲诱导的致病的基础.
主要方法:
- 人类支气管上皮细胞 (BEAS-2B) 暴露于低 (100微米) 和高 (500微米) 的甲剂量.
- 使用基于高分辨率液体染色学-并联质谱的蛋白质学分析了基斯提取物.
- 进行了PTM组合分析和单个PTM部位/类型比较.
主要成果:
- 甲基甲暴露导致了组素H3和H4甲基化和乙化模式的显著改变.
- 具体的修改包括H3K4和H3K79的低甲基化,以及其他多个H3和H4位点的变化.
- 这些FA诱导的组织蛋白修饰反映了在癌症和神经退行性疾病 (如阿尔茨海默氏症) 中观察到的基因组修饰.
结论:
- 甲暴露会导致系统性表观遗传变化,导致组织甲基化和乙化.
- 这些发现为甲的表观遗传毒性提供了新的证据.
- 这项研究为形式甲驱动的病变发生机制提供了新的见解.
相关概念视频
Histone Modification
12.9K
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...
12.9K
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
Spreading of Chromatin Modifications
8.2K
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...
8.2K
Inheritance of Chromatin Structures
6.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.2K
Chromatin Modification in iPS Cells
1.6K
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...
1.6K
Covalently Linked Protein Regulators
6.7K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.7K


