基因表达的代谢调节
Di Zhang1, Zhanyun Tang2, He Huang1,3
1Ben May Department for Cancer Research, The University of Chicago, Chicago, IL, USA.
Nature
|October 25, 2019
概括
乳酸盐以其代谢作用而闻名,也起到表观遗传修饰的作用. 乳酸基因的乳化直接刺激基因转录,揭示了细胞过程和癌症等疾病的新见解.
科学领域:
- 生物化学
- 表观遗传学
- 细胞生物学
背景情况:
- 沃伯格效应描述了癌症中乳酸的增加,并与瘤和败血症等疾病有关.
- 乳酸盐主要作为能量来源和代谢副产品,但其非代谢功能在很大程度上是未知的.
- 了解乳酸的不同作用对于了解各种病理生理条件至关重要.
研究的目的:
- 研究乳酸在细胞过程中的非代谢功能.
- 探索乳酸作为表观遗传修饰剂的作用.
- 阐明乳酸影响基因转录的机制.
主要方法:
- 在人体和小鼠细胞中确定核心组织蛋白的乳化部位.
- 在低氧和细菌刺激条件下通过糖分解诱导乳酸盐的产生.
- 在细菌暴露期间对M1巨细胞的基因素乳化动态进行分析,并与乙化进行比较.
主要成果:
- 鉴定出由乳酸盐衍生的基因组氨酸残留物是表观遗传修饰.
- 在人体和小鼠细胞中发现了28个核心基因素的乳酸位.
- 由低氧和细菌挑战诱导的基因乳化,作为基因转录的前体.
- 与M1巨细胞中的乙化相比,基因组乳化表现出不同的时间动态.
- 晚期M1巨极化中素乳化增加可调节Arg1等恒常性和伤口愈合基因.
结论:
- 乳酸基因的乳化直接刺激基因转录从染色体.
- 在M1巨中,一种内源的"乳酸时钟"在细菌挑战过程中调节同质化的基因表达.
- 在生理学和疾病,包括感染和癌症中,乳酸的功能提供了新的视角.
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