内基因DNA甲基化可以防止伪转录的启动
Francesco Neri1,2, Stefania Rapelli3, Anna Krepelova1,3
1Human Genetics Foundation (HuGeF), via Nizza 52, 10126 Torino, Italy.
Nature
|February 23, 2017
概括
由Dnmt3b驱动的基因体DNA甲基化可以防止小鼠细胞中不必要的转录启动. 这种表观遗传机制确保了基因表达的准确性,并且可能与癌症有关.
科学领域:
- 表观遗传学
- 分子生物学
- 基因组学
背景情况:
- 在哺乳动物中,DNA甲基化主要发生在CpG位点.
- 促进物甲基化会抑制基因表达,但基因体甲基化的作用尚不清楚.
- 了解基因体甲基化对于基因调节和疾病至关重要.
研究的目的:
- 研究高度表达基因内基因甲基化的功能.
- 阐明基因体甲基化调节转录的机制.
- 探索表观遗传过程与癌症之间的联系.
主要方法:
- 在小鼠胚胎干细胞中进行全基因组DNA甲基化分析.
- 对H3K36me3进行染色体免疫沉测序 (ChIP-seq).
- 对RNA聚合酶II活性和伪转录的分析.
- 对Dnmt3b的酶活性测定
主要成果:
- 在基因体中依赖Dnmt3b的DNA甲基化阻止了假RNA聚合酶II的进入.
- 这一过程由H3K36三甲基化 (H3K36me3) 和Dnmt3b的酶活性介导.
- 异常转录被降解或转化为非功能性蛋白质.
- 涉及SetD2,H3K36me3,Dnmt3b和DNA甲基化的表观基因交叉声确保了转录的真实性.
结论:
- 内基因DNA甲基化作为对加密转录启动的保护措施.
- 这种表观遗传机制对于保持转录精度至关重要.
- 这种途径的失调,包括内基因低甲基化,对癌症的发展有影响.
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