G-Quadruplex DNA- and RNA-Specific-Binding Proteins Engineered from the RGG Domain of TLS/FUS
G-Quadruplex DNA- and RNA-Specific-Binding Proteins Engineered from the RGG Domain of TLS/FUS
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DOI：
10.1021/acschembio.5b00566
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发表时间：
2015-11-01
影响因子：
4
通讯作者：
Oyoshi, Takanori
中科院分区：
文献类型：
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作者：
Takahama, Kentaro;Miyawaki, Arisa;Oyoshi, Takanori
人端粒DNA（Htelo）和含端粒重复序列的RNA（TERRA）是端粒的组成部分，分别含有短DNA重复序列d（TTAGGG）和RNA重复序列r（UUAGGG）。Htelo和TERRA形成G-四链体，但它们在端粒中形成G-四链体的生物学意义尚不清楚。选择性结合G-四链体DNA和RNA的化合物可用于理解每个G-四链体的功能。在这里，我们报告，工程Arg-Gly-Gly重复（RGG）结构域的易位脂肪肉瘤中只含有苯丙氨酸（RGGF）和酪氨酸（RGGY）特异性结合和稳定的G-四链体的Htelo和TERRA，分别。此外，RGGF抑制端粒中组蛋白H4在赖氨酸20和组蛋白H3在赖氨酸9的三甲基化，而RGGY仅抑制活细胞中的H3三甲基化。这些发现表明，G-四链体的Htelo和TERRA在端粒组蛋白甲基化有不同的功能。
Human telomere DNA (Htelo) and telomeric repeat-containing RNA (TERRA) are integral telomere components containing the short DNA repeats d(TTAGGG) and RNA repeats r(UUAGGG), respectively. Htelo and TERRA form G-quadruplexes, but the biological significance of their G-quadruplex formation in telomeres is unknown. Compounds that selectively bind G-quadruplex DNA and RNA are useful for understanding the functions of each G-quadruplex. Here we report that engineered Arg-Gly-Gly repeat (RGG) domains of translocated in liposarcoma containing only Phe (RGGF) and Tyr (RGGY) specifically bind and stabilize the G-quadruplexes of Htelo and TERRA, respectively. Moreover, RGGF inhibits trimethylation of both histone H4 at lysine 20 and histone H3 at lysine 9 at telomeres, while RGGY inhibits only H3 trimethylation in living cells. These findings indicate that G-quadruplexes of Htelo and TERRA have distinct functions in telomere histone methylation.