通过4-oxo-2-nonenal进行稳定基因组添加:氧化应激和表观遗传学之间的潜在联系
James J Galligan1, Kristie L Rose, William N Beavers
1A. B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of †Biochemistry, ‡Chemistry, and §Pharmacology, ∥Mass Spectrometry Research Center, ⊥Center in Molecular Toxicology, and #Cell and Developmental Biology, Vanderbilt Institute of Chemical Biology, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine , Nashville, Tennessee 37232-0146, United States.
Journal of the American Chemical Society
|August 8, 2014
概括
像4-oxo-2-nonenal这样的脂质电友会改变组织蛋白,影响细胞功能. 这些组素修饰,特别是在H3K27中,破坏了核细胞组合,揭示了脂质电友研究的新目标.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 脂质电友是可以修改细胞蛋白的反应分子.
- 基因组是参与DNA包装和调节的关键蛋白质.
研究的目的:
- 为了识别和表征由脂质电友4-oxo-2-nonenal. histones的修饰.
- 研究这些基因组修饰对核细胞组合的功能后果.
主要方法:
- 从完整的细胞中分离染色素.
- 通过质谱学识别 histone 添加物.
- 在修改后的基因组的存在下,核细胞组合的分析.
主要成果:
- 鉴定了基因组的七个 adducts,包括四个4-ketoamides在lysine和三个迈克尔在histidine的 adducts.
- 在刺激的巨细胞中发现了H3K27的特定的4-胺添加物.
- 基因组H3和H4通过4-oxo-2-nonenal抑制核细胞组合的修饰.
结论:
- 基质子是4-oxo-2-nonenal修改的重要目标.
- 这些修改导致稳定的添加物,类似于已知的基因素化.
- 观察到的核细胞组合抑制突出了一个新的机制,即脂质电友可以改变染色体结构和功能.
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