基因素H3K18和H3K23的乙化指导着MLL介导的H3K4甲基化的建立
Geoffrey C Fox1, Karl F Poncha2, B Rutledge Smith3
1Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
The Journal of biological chemistry
|July 3, 2024
概括
在H3K18和H3K23的基因组乙化强烈刺激MLL复合体的H3K4甲基化. 这解释了基因素乙化和活性基因表达之间的联系.
科学领域:
- 表观遗传学和基因调控
- 染色体生物学 染色体生物学
- 转录的分子机制的转录
背景情况:
- 基因组N端尾与DNA相互作用,限制对DNA和修饰部位的访问.
- 希斯乙化中和正电荷,破坏DNA-尾巴相互作用并提高可访问性.
- 之前的研究发现了MLL1.1对H3K4me3的聚乙化介导的染色体开关.
研究的目的:
- 为了确定H3尾部乙化位点对H3K4甲基化的特定贡献.
- 为了研究H3尾部乙化对其他染色质修饰剂的影响.
- 阐明MLL复合物的H3尾化和H3K4甲基化之间的关系.
主要方法:
- 基因素H3 N-终端尾部的局部特异性乙化分析.
- 通过MLL1和MLL4复合体测量H3K4甲基化活性的试验.
- 对H3K4me1/me3与特定的H3乙化蛋白质形式进行联合丰富分析.
- 测试其他基因组修饰酶对H3尾部乙化反应的敏感性.
主要成果:
- H3K18和H3K23的乙化显示出对MLL1和MLL4.4的H3K4甲基化具有显著的刺激作用.
- H3K4me1和H3K4me3优先与在K18和K23 (H3{K18acK23ac}) 两处都被乙化的H3蛋白形式共同丰富.
- H3K4甲基化通过尾部乙化得到独特的刺激,与H3K9,H3K27,H3K36,H3K79或H3T3.3.9的修饰不同.
结论:
- H3K18和H3K23的乙化独特而强烈地刺激了H3K4的甲基化.
- 这种依赖于乙化的刺激提供了对H3K4甲基化与活性基因表达的关联的洞察.
- 这些发现突显出一种特定的调节机制,涉及素乙化和H3K4甲基化.
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