Dido3 PHD modulates cell differentiation and division.
Dido3 PHD modulates cell differentiation and division.
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DOI：
10.1016/j.celrep.2013.06.014
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发表时间：
2013-07-11
期刊：
影响因子：
8.8
通讯作者：
Kutateladze TG
中科院分区：
文献类型：
--
作者：
Gatchalian J;Fütterer A;Rothbart SB;Tong Q;Rincon-Arano H;Sánchez de Diego A;Groudine M;Strahl BD;Martínez-A C;van Wely KH;Kutateladze TG
死亡诱导剂 Obliterator 3 (Dido3) 与干细胞基因组稳定性的维持和肿瘤发生有关。在这里，我们发现 Dido3 通过其植物同源结构域 (PHD) 指调节胚胎干细胞中干性基因的表达。 Dido3 PHD 与组蛋白 H3K4me3 的结合会被苏氨酸磷酸化破坏，从而触发 Dido3 从染色质易位到有丝分裂纺锤体。 Dido3 PHD 与 H3K4me3 复合物的晶体结构揭示了一个包含组氨酸残基的非典型芳香族笼状结合位点。对结合机制的生化、结构和突变分析确定了特异性和亲和力的决定因素，并解释了同源 PHF3 无法结合 H3K4me3。总之，我们的研究结果揭示了胚胎发育中的转录控制与细胞分裂调节之间的联系。
Death Inducer Obliterator 3 (Dido3) is implicated in the maintenance of stem cell genomic stability and tumorigenesis. Here, we show that Dido3 regulates the expression of stemness genes in embryonic stem cells through its plant homeodomain (PHD) finger. Binding of Dido3 PHD to histone H3K4me3 is disrupted by threonine phosphorylation that triggers Dido3 translocation from chromatin to the mitotic spindle. The crystal structure of Dido3 PHD in complex with H3K4me3 reveals an atypical aromatic-cage-like binding site that contains a histidine residue. Biochemical, structural, and mutational analyses of the binding mechanism identified the determinants of specificity and affinity and explained the inability of homologous PHF3 to bind H3K4me3. Together, our findings reveal a link between the transcriptional control in embryonic development and regulation of cell division.