Crystal structures of REF6 and its complex with DNA reveal diverse recognition mechanisms
Crystal structures of REF6 and its complex with DNA reveal diverse recognition mechanisms
复制标题
REF6 及其与 DNA 的复合物的晶体结构揭示了多种识别机制。
DOI：
10.1038/s41421-020-0150-6
复制
发表时间：
2020
期刊：
影响因子：
33.5
通讯作者：
Zhongzhou Chen
中科院分区：
文献类型：
--
作者：
Zizi Tian;Xiaorong Li;Min Li;Wei Wu;Manfeng Zhang;Chenjun Tang;Zhihui Li;Yunlong Liu;Zhenhang Chen;Meiting Yang;Lulu Ma;Cody Caba;Yufeng Tong;Hon-Ming Lam;Shaodong Dai;Zhongzhou Chen
Relative of Early Flowing 6（REF 6）是一种DNA序列特异性的H3 K27 me 3/2去甲基化酶，含有4个锌指结构域，靶向拟南芥中的数千个基因。ZnF结构域是结合靶基因所必需的，但其结构基础尚不清楚。在这里，我们确定了ZnF结构域和REF 6-DNA复合物的晶体结构，揭示了一个独特的REF 6家族特异性的半交叉支撑ZnF（RCZ）结构域和两个C2 H2型ZnF。DNA结合诱导REF 6铰链区的深刻构象变化。每个REF 6识别六个碱基，DNA甲基化降低了结合亲和力。酸性区域和碱性区域对REF 6的自缔合都很重要。REF 6 DNA结合亲和力由DNA的序列依赖性构象以及不同靶基序中的协同性决定。构象可塑性使REF 6能够作为一个全局转录调节因子，直接与许多不同的基因结合，揭示了表观遗传修饰识别的结构基础。
Relative of Early Flowing 6 (REF6) is a DNA-sequence-specific H3K27me3/2 demethylase that contains four zinc finger (ZnF) domains and targets several thousand genes inArabidopsis thaliana. The ZnF domains are essential for binding target genes, but the structural basis remains unclear. Here, we determined crystal structures of the ZnF domains and REF6-DNA complex, revealing a unique REF6-family-specific half-cross-braced ZnF (RCZ) domain and two C2H2-type ZnFs. DNA-binding induces a profound conformational change in the hinge region of REF6. Each REF6 recognizes six bases and DNA methylation reduces the binding affinity. Both the acidic region and basic region are important for the self-association of REF6. The REF6 DNA-binding affinity is determined by the sequence-dependent conformations of DNA and also the cooperativity in different target motifs. The conformational plasticity enables REF6 to function as a global transcriptional regulator that directly binds to many diverse genes, revealing the structural basis for the epigenetic modification recognition.