Polycomb repressive complex 2 (PRC2-EZH2) methylates histone H3 at lysine 27 (H3K27) and is required to maintain gene repression during development. Misregulation of PRC2 is linked to a range of neoplastic malignancies, which is believed to involve methylation of H3K27. However, the full spectrum of non-histone substrates of PRC2 that might also contribute to PRC2 function is not known. We characterized the target recognition specificity of the PRC2 active site and used the resultant data to screen for uncharacterized potential targets. The RNA polymerase II (Pol II) transcription elongation factor, Elongin A (EloA), is methylated by PRC2 in vivo. Mutation of the methylated EloA residue decreased repression of a subset of PRC2 target genes as measured by both steady-state and nascent RNA levels and perturbed embryonic stem cell differentiation. We propose that PRC2 modulates transcription of a subset of low expression target genes in part via methylation of EloA.

聚梳阻遏复合物2（PRC2-EZH2）使赖氨酸27（H3K27）处的组蛋白H3甲基化，并且在发育过程中需要维持基因阻抑。PRC2的失调与一系列恶性肿瘤有关，据信这涉及H3K27的甲基化。但是，PRC2的非组蛋白底物的全谱也可能对PRC2的功能有贡献，这一点尚不清楚。我们表征了PRC2活性位点的目标识别特异性，并使用所得数据筛选了未表征的潜在目标。RNA聚合酶II（Pol II）转录延伸因子Elongin A（EloA）在体内被PRC2甲基化。甲基化的EloA残基的突变降低了PRC2目标基因的一个子集的阻抑，这是通过稳态和新生RNA水平以及扰动的胚胎干细胞分化来衡量的。我们建议PRC2部分通过EloA的甲基化调节低表达靶基因子集的转录。