H3K79甲基化和H3K36三甲基化协同调节多能干细胞中的基因表达
Emmalee W Cooke1, Cheng Zeng1,2, Suza Mohammad Nur1,2
1Department of Biochemistry, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA.
Science advances
|July 4, 2025
概括
这项研究揭示了H3K79甲基化和H3K36三甲基化在基因调节和细胞分化中的协同作用. 破坏这些表观遗传标记会导致超转录和神经发育受损.
科学领域:
- 表观遗传学和基因调控
- 分子生物学分子生物学
- 发育生物学 发展生物学
背景情况:
- 由DOT1L沉积的H3K79甲基化,在活性基因上发现,但其确切作用尚不清楚.
- DOT1L与白血病和神经系统疾病有关,强调需要了解H3K79me的功能.
研究的目的:
- 研究H3K79甲基化和H3K36三甲基化在基因表达和细胞分化中的功能协同作用.
- 阐明这种协同作用背后的分子机制及其对疾病的影响.
主要方法:
- 同时催化不活化DOT1L和SETD2 (H3K36甲基转移酶).
- 对基因表达,染色质可访问性和转录延长的分析.
- 研究了转录因子YAP-TEAD对增强剂的招募.
主要成果:
- 丢失H3K79me/H3K36me3导致过度活跃的转录和失败的神经分化.
- 这种损失导致了转录延长的增加,并提高了增强剂的染色质可访问性.
- 抑制YAP-TEAD通路恢复了正常的基因表达水平.
结论:
- H3K79me和H3K36me3协同作用,调节转录和细胞命运.
- YAP-TEAD通路是H3K79me/H3K36me3损失的影响的关键调解者.
- 结果提供了针对涉及DOT1L和SETD2错误调节的疾病的见解.
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