Blazer Levi L, Lima-Fernandes Evelyne, Gibson Elisa, Eram Mohammad S, Loppnau Peter, Arrowsmith Cheryl H, Schapira Matthieu, Vedadi Masoud
From the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
From the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, the Princess Margaret Cancer Centre and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, and.
J Biol Chem. 2016 Jun 24;291(26):13509-19. doi: 10.1074/jbc.M116.721472. Epub 2016 Apr 29.
PR domain-containing protein 7 (PRDM7) is a primate-specific histone methyltransferase that is the result of a recent gene duplication of PRDM9. The two proteins are highly homologous, especially in the catalytic PR/SET domain, where they differ by only three amino acid residues. Here we report that PRDM7 is an efficient methyltransferase that selectively catalyzes the trimethylation of H3 lysine 4 (H3K4) both in vitro and in cells. Through selective mutagenesis we have dissected the functional roles of each of the three divergent residues between the PR domains of PRDM7 and PRDM9. These studies indicate that after a single serine to tyrosine mutation at residue 357 (S357Y), PRDM7 regains the substrate specificities and catalytic activities similar to its evolutionary predecessor, including the ability to efficiently methylate H3K36.
含PR结构域蛋白7（PRDM7）是一种灵长类特异性组蛋白甲基转移酶，它是PRDM9近期基因复制的产物。这两种蛋白质高度同源，尤其是在催化性PR/SET结构域，它们在该结构域仅相差三个氨基酸残基。在此我们报告，PRDM7是一种高效的甲基转移酶，在体外和细胞内均能选择性催化组蛋白H3赖氨酸4（H3K4）的三甲基化。通过选择性诱变，我们剖析了PRDM7和PRDM9的PR结构域之间三个不同残基各自的功能作用。这些研究表明，在第357位残基（S357Y）发生单个丝氨酸到酪氨酸的突变后，PRDM7恢复了与其进化前身相似的底物特异性和催化活性，包括有效甲基化H3K36的能力。
