由三种Drosophila甲基转移酶对基因组上下文依赖的素H3K36甲基化以及对专用染色体读取器的含义
Muhunden Jayakrishnan1, Magdalena Havlová2, Václav Veverka2,3
1Biomedical Center, Molecular Biology Division, Ludwig-Maximilians-Universität, Munich, Germany.
Nucleic acids research
|May 30, 2024
概括
基因组H3氨酸36甲基化 (H3K36me) 有不同的作用. 不同的甲基化状态 (K36me1,K36me2,K36me3) 定义了特定的染色质状态,影响了表观遗传读者结合和基因调节.
科学领域:
- 表观遗传学和染色体生物学
- 分子生物学分子生物学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 基因组H3 lysine 36甲基化 (H3K36me) 是与活性染色体相关的关键表观遗传标记,并由读者蛋白解释.
- 像MSL3和JASPer这样的蛋白质结合H3K36me3,影响基因转录和染色质完整性.
- 之前的研究表明H3K36me3是主要标记,但其枯竭显示出对读者互动的位置特异性影响,促使进一步调查.
研究的目的:
- 系统地研究H3K36me1,H3K36me2和H3K36me3在定义色素状态中的不同作用.
- 描述全基因组甲基化场景和甲基转移酶Set2,NSD和Ash1的功能.
- 确定表观遗传阅读器MSL3和JASPer对不同H3K36甲基化状态的结合特异性.
主要方法:
- 在细胞模型中甲基转移酶 (Set2,NSD,Ash1) 的耗尽,以分析H3K36甲基化场景.
- 对H3K36甲基化状态的全基因组映射以及读者MSL3和JASPer的分布.
- 直接亲和度测量以确认读者绑定特征.
主要成果:
- 每个H3K36me1,H3K36me2和H3K36me3都导致了不同的染色质状态,挑战了当前的模型.
- 设置2主要催化H3K36me3在euchromatin,NSD沉积H3K36me2/3在异性染色质和弱性染色质,和Ash1沉积H3K36me1在增强器区域.
- MSL3和JASPer结合了H3K36me2和H3K36me3,扩大了它们的目标位置并提高了它们的功能稳定性.
结论:
- H3K36甲基化场景比以前认为的要复杂得多,每个甲基化状态都有不同的作用.
- 特定的甲基转移酶在不同的基因组区域储存独特的H3K36甲基化模式,为多样化的染色质功能做出贡献.
- 读者MSL3和JASPer对H3K36me2和H3K36me3的双重特异性增加了表观遗传调节的精度和范围.
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