Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Laboratory for Phyloinformatics, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
Elife. 2020 Sep 1;9:e58675. doi: 10.7554/eLife.58675.
The Polycomb repressive complex 2 (PRC2) is a multicomponent histone H3K27 methyltransferase complex, best known for silencing the 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 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 H3t 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.
多梳抑制复合物 2（PRC2）是一种多组分组蛋白 H3K27 甲基转移酶复合物，在胚胎发育过程中通过沉默基因而闻名。Polycomb 样蛋白 PHF1、MTF2 和 PHF19 是 PRC2 的关键组成部分，通过在胚胎干细胞中刺激其催化活性。先前已经表明 PHF1/19 的 Tudor 结构域在体外是 H3K36me3 的读取器。然而，一些其他研究表明，PHF1 和 PHF19 在细胞内与 H3K27me3 标记共定位，但不与 H3K36me3 共定位。在这里，我们提供了进一步的证据表明 PHF1 与 H3t 在睾丸中共定位，并且其 Tudor 结构域在体外优先结合 H3tK27me3 而不是经典的 H3K27me3。我们的 PHF1 和 PHF19 的 Tudor 结构域与 H3tK27me3 的复合物结构阐明了 PHF1 和 PHF19 对 H3tK27me3 的优先识别的分子基础，暗示 H3tK27me3 可能是 PHF1/19 的生理配体。
