通过RNA聚合酶II延长复合体识别5 - 碳氧细胞蛋白的分子基础
Lanfeng Wang1, Yu Zhou2, Liang Xu1
1Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Nature
|July 1, 2015
概括
在转录过程中,氧化DNA基,5-formylcytosine (5fC) 和5-carboxylcytosine (5caC) 直接阻碍RNA聚合酶II (Pol II). 这种结构相互作用揭示了Pol II.
科学领域:
- 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
- 结构生物学 结构生物学
背景情况:
- 基因甲基化 (5-甲基细胞素,5mC) 和脱甲基化对胚胎发育至关重要.
- TET酶产生氧化的5mC衍生物:5-基甲基细胞因子 (5hmC),5-甲基细胞因子 (5fC) 和5-基细胞因子 (5caC).
- 5fC和5caC影响基因表达的确切机制在很大程度上是未知的.
研究的目的:
- 阐明氧化5-甲基氨酸衍生物如何影响转录的结构基础.
- 研究高5fC和5caC水平对基因表达的体内功能影响.
主要方法:
- 酵母RNA聚合酶II (Pol II) 的X射线晶体学复杂化与修改后的DNA.
- 在增加5fC/5caC水平的条件下,体内转录的全球分析.
主要成果:
- 晶体结构揭示了5caC和Pol II epi-DNA识别循环之间的特定键.
- 这种相互作用导致Pol II的结构变化,阻碍了核酸的添加,并影响了延长.
- 在体内研究证实,增加的5fC/5caC水平显著减缓了基因体上的Pol II延长.
结论:
- 氧化5-甲基细胞因子衍生物通过改变Pol II的结构和功能,直接影响转录延长.
- RNA聚合酶II作为直接的表观遗传传感器,在转录过程中对DNA修改作出反应.
- 这些发现为DNA氧化在基因表达中的调节作用提供了新的见解.
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