近日,，北京生命科學(xué)研究所朱冰實(shí)驗(yàn)室2011年發(fā)表于The Journal of Biological chemistry上的文章“H3K36 methylation antagonizes PRC2 mediated H3K27 methylation”近日被評(píng)為The Journal of Biological chemistry 2011年度最佳論文。
在朱冰去年的研究論文中,，作者主要報(bào)道了組蛋白H3第36位賴氨酸甲基化可以拮抗組蛋白甲基化酶PRC2對(duì)H3第27位賴氨酸進(jìn)行修飾,。PRC2復(fù)合物所介導(dǎo)的組蛋白H3第27位賴氨酸甲基化修飾對(duì)于基因的轉(zhuǎn)錄起著重要的調(diào)節(jié)作用。PRC2復(fù)合物所介導(dǎo)的27位賴氨酸甲基化修飾可以在染色質(zhì)上蔓延從而形成區(qū)域性的抑制型染色質(zhì)環(huán)境,。所以,，一個(gè)很重要的問(wèn)題就是染色質(zhì)上哪些組分能夠拮抗這種蔓延。在本項(xiàng)研究中我們發(fā)現(xiàn)在HeLa細(xì)胞中,，H3第27位賴氨酸的三甲基化修飾很少與H3第36賴氨酸的高階甲基化（二甲基化合三甲基化）修飾共存于同一條多肽上,。并且通過(guò)生化實(shí)驗(yàn)證明含有H3第36位賴氨酸甲基化修飾的核小體可以抑制PRC2復(fù)合物在其上的活性,。最后，我們還證明了一個(gè)已知的PRC2拮抗蛋白ASH1,，是一個(gè)H3第36位賴氨酸專一性的組蛋白甲基化酶,。
The Journal of Biological Chemistry以工作的出色程度及其對(duì)研究領(lǐng)域潛在的深遠(yuǎn)影響為標(biāo)準(zhǔn)，對(duì)2011年全年發(fā)表在該雜志上的4000多篇文章進(jìn)行評(píng)選,，最終評(píng)選出20篇2011年度最佳論文,。
該論文的共同第一作者是袁文博士和徐墨博士。論文的其他作者還包括我所博士生黃暢和劉楠,，以及蛋白質(zhì)中心陳涉博士,。朱冰博士是論文的通訊作者。該項(xiàng)目由科技部和北京市資助,，完成于北京生命科學(xué)研究所,。（生物谷Bioon.com）
Bioon 2011年報(bào)道
The Journal of Biological Chemistry 2011年度最佳論文
doi:10.1074/jbc.M110.194027
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H3K36 methylation antagonizes PRC2 mediated H3K27 methylation
Wen Yuan1, Mo Xu2, Chang Huang1, Nan Liu3, She Chen4 and Bing Zhu4,*
H3K27 methylation mediated by the histone methyltransferase complex PRC2 is critical for transcriptional regulation, Polycomb silencing, Drosophila segmentation, mammalian X chromosome inactivation and cancer. PRC2-mediated H3K27 methylation can spread along the chromatin and propagate the repressive chromatin environment; thus, chromatin components that antagonize PRC2's activity are important for restraining Polycomb silencing. Here we report that in HeLa cells, H3 histones unmethylated at K36 are mostly methylated at K27, with the exception of newly synthesized H3. In addition, K27me3 rarely co-exists with K36me2 or K36me3 on the same histone H3 polypeptide. Moreover, PRC2 activity is greatly inhibited on nucleosomal substrates with pre-installed H3K36 methylation. These findings collectively identify H3K36 methylation as a chromatin component that restricts the PRC2-mediated spread of H3K27 methylation. Finally, we provide evidence that the controversial histone lysine methyltransferase Ash1, a known Trithorax group protein that antagonizes Polycomb silencing in vivo, is an H3K36-specific dimethylase, not an H3K4 methylase, further supporting the role of H3K36 methylation in antagonizing PRC2-mediated H3K27 methylation.
