MLL4 结合了 TET3 的结合
Dustin C Becht1, Sk Abdul Mohid2, Ji-Eun Lee3
1Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Structure (London, England : 1993)
|April 5, 2024
概括
混合血统白血病4 (MLL4) 通过其PHD6手指与十一转位3 (TET3) 相互作用. 这种相互作用发生在活性增强剂上,表明MLL4和TET3在基因调节中的功能联系.
科学领域:
- 表观遗传学和转录的调节.
- 在基因表达中的蛋白质-蛋白质相互作用.
- 生物化学和结构生物学.
背景情况:
- 混合血统白血病4 (MLL4),也称为KMT2D,对于增强器激活和细胞类型特定转录至关重要.
- MLL4有一个催化域和七个植物本地域 (PHD) 指,后者的特征是有限的.
- 十-十一转位3 (TET3) 是一种参与DNA脱甲基化的二氧化酶,将甲基化氨酸转化为氧化形式.
研究的目的:
- 调查MLL4和TET3.3之间的相互作用.
- 阐明MLL4-TET3结合的结构基础.
- 探索这种相互作用在基因调节中的功能影响.
主要方法:
- 解决方案核磁共振 (NMR) 对TET3-MLL4 PHD6复合体的结构确定.
- 生物化学结合测试以表征相互作用.
- 在小鼠胚胎干细胞中对MLL4和TET3进行基因组定位分析.
主要成果:
- MLL4 (MLL4 PHD6) 的第六个PHD指直接与TET3.3上的疏水动机结合.
- 结构分析显示,TET3占据了MLL4 PHD6上的一处疏水部位,类似于基因素H4.
- 这种相互作用在MLL3的第七个PHD指 (MLL3 PHD7) 中得到保护.
- 内源性MLL4和异位表达的TET3在它们在活性增强剂上的基因组定位上显著重叠.
结论:
- MLL4 PHD6通过保留的疏水性结合点与TET3相互作用.
- 重叠的基因组分布表明,在活性增强剂中,MLL4和TET3之间存在功能关系.
- 这种相互作用可能在协调表观遗传修饰和DNA脱甲基化中发挥作用,用于转录控制.
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