较小的65K/RNPC3结合体与ANKRD11相互作用,并调解HDAC3-调节的素脱乙和转录
Chen-Hui Li1, Shao-Bo Liang1, Qi-Wei Huang1
1RNA Institute, State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Science, TaiKang Center for Life and Medical Sciences, Wuhan University, Hubei, 430072, China.
概括
这项研究揭示了小结合体和基因素脱甲基化之间的新联系. 小结合体组件65K (KiloDalton) 与ANKRD11相互作用,ANKRD11是一种基因素脱乙酶3 (HDAC3) 辅因子,影响基因表达调节.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因规则 基因规则
背景情况:
- RNA拼接对于基因表达至关重要,涉及复杂的核相互作用.
- 虽然主要结合体的作用已经确立,但小结合体的功能仍然不太了解.
- 基因脱乙化是调节基因表达的关键表观遗传机制.
研究的目的:
- 在基因调控中研究小结合体的功能相互作用.
- 为了确定小配合体组件的新型蛋白质合作伙伴.
- 阐明将小结合体功能与表观遗传修饰联系在一起的机制.
主要方法:
- 在Drosophila溶解物中进行亲和性净化,以识别相互作用的蛋白质.
- CRISPR/Cas9基因编辑以创建删除突变 (Dm65KΔ/Δ和Dmankrd11Δ/Δ) 的基因.
- 在人体细胞中的目标和标记 (CUT&Tag) 试验下的分离.
- 基因素脱乙烯化试验 (H3K9和H4K5).
主要成果:
- 在小结合体65K (KiloDalton) 和ANKRD11之间确定了一种相互作用,ANKRD11是3 (HDAC3) 基因素脱乙酶的辅因子.
- 缺少Dm65K或Dmankrd11的突变体在Drosophila中表现出减少的素脱甲基化和神经缺陷.
- ANKRD11充当桥梁因子,促进HDAC3和65K的协同色素结合,这对H3K9脱乙和基因表达至关重要.
结论:
- 一个新的,保守的机制将基因脱乙烯化与小结合体结合在一起,用于基因表达调节.
- 65K-ANKRD11-HDAC3复合体在表观遗传控制中发挥着重要作用.
- 这一发现扩大了我们对前mRNA处理之外的结合体功能的理解.
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