Structural basis for histone variant H3tK27me3 recognition by PHF1 and PHF19
Structural basis for histone variant H3tK27me3 recognition by PHF1 and PHF19
复制标题
PHF1 和 PHF19 识别组蛋白变体 H3tK27me3 的结构基础
DOI：
10.7554/elife.58675
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发表时间：
2020-09-01
期刊：
影响因子：
7.7
通讯作者：
Min, Jinrong
中科院分区：
文献类型：
--
作者：
Dong, Cheng;Nakagawa, Reiko;Min, Jinrong
PRC 2（Polycomb repressive complex 2）复合物是一种多组分组蛋白H3 K27甲基转移酶，以在胚胎发育期间沉默Hox基因而闻名。Polycomb样蛋白PHF 1、MTF 2和PHF 19通过刺激PRC 2在胚胎干（ES）细胞中的催化活性而成为PRC 2的关键组分。PHF 1/19的Tudor结构域先前已被证明是H3 K36 me 3的体外阅读器。然而，其他一些研究表明，PHF 1和PHF 19与H3 K27 me 3标记共定位，而不是H3 K36 me 3在细胞中。在这里，我们提供了进一步的证据表明，PHF 1与H3 tK 27在睾丸中共定位，其Tudor结构域在体外优先结合H3 tK 27 me 3而不是典型的H3 K27 me 3。我们的PHF 1和PHF 19的Tudor结构域与H3 tK 27 me 3的复杂结构揭示了PHF 1和PHF 19优先识别H3 tK 27 me 3的分子基础，这意味着H3 tK 27 me 3可能是PHF 1/19的生理配体。
The PRC2 (Polycomb repressive complex 2) complex is a multi-component histone H3K27 methyltransferase, best known for silencing Hox genes during embryonic development. The Polycomb-like proteins PHF1, MTF2 and PHF19 are critical components of PRC2 by stimulating its catalytic activity in embryonic stem (ES) cells. The Tudor domains of PHF1/19 have been previously shown to be readers of H3K36me3 in vitro. However, some other studies suggest that PHF1 and PHF19 co-localize with the H3K27me3 mark, but not H3K36me3 in cells. Here, we provide further evidence that PHF1 co-localizes with H3tK27 in testis, and its Tudor domain preferentially binds to H3tK27me3 over canonical H3K27me3 in vitro. Our complex structures of the Tudor domains of PHF1 and PHF19 with H3tK27me3 shed light on the molecular basis for preferential recognition of H3tK27me3 by PHF1 and PHF19 over canonical H3K27me3, implicating that H3tK27me3 might be a physiological ligand of PHF1/19.