组蛋白H3第四位赖氨酸的甲基化(H3K4me)对真核生物转录活性的染色体的形成是至关重要的。
组蛋白H2B单泛素化(H2Bub1)是另一个与转录有关的组蛋白修饰。研究发现，在酵母、果蝇以及一些人类细胞系，H3K4me通过H2Bub1被全面的刺激。
目前，这些反式的组蛋白修饰通路的机制还不明确，但是对不同的实验系统进行的研究表明，H2Bub1能够影响甲基转移酶复合体的亚基构成或是直接激活甲基转移酶的活性。
来自加拿大麦吉尔大学的研究人员已经在体外重新构建了这个通路，他们使用来自裂殖酵母的H3K4特异性甲基转移酶复合体Set1C，以及含有半合成的H2Bub1的染色质底物。
实验结果发现，在体外裂殖酵母的Set1C对核小体组蛋白H3的活性通过H2Bub1被直接增强。
重要的是，来源于缺失H2Bub1细胞的Set1C保留了对自由的组蛋白底物的活性，这表明在没有H2Bub1时Set1C保持完好。
染色质免疫沉淀分析显示，在H2Bub1缺陷的突变体，招募完好的Set1C到转录的染色质的过程也是缺陷的。
该实验讨论了裂殖酵母组蛋白窜扰（crosstalk）与Set1C甲基化转移酶活性通过H2Bub1的作用直接增强的关系，表明H2Bub1-H3K4me窜扰在真核生物中是保守的。相关论文发表在4月13日的Journal of Biological Chemistry。（生物谷Deepblue编译）
doi: 10.1074/jbc.M112.356253
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Histone H2B ubiquitylation promotes activity of the intact Set1 histone methyltransferase complex in fission yeast
Ariane Racine, Viviane Page, Stephen Nagy, David Grabowski and Jason C. Tanny.
The methylation of histone H3 on lysine 4 (H3K4me) is critical for the formation of transcriptionally active chromatin in eukaryotes.In yeast, Drosophila, and some human cell lines, H3K4me is globally stimulated by the mono-ubiquitylation of histone H2B (H2Bub1), another histone modification associated with transcription.The mechanism of this trans-histone modification pathway remains uncertain, and studies carried out in different experimental systems have suggested that H2Bub1 could either influence the subunit composition of methyltransferase complexes or directly stimulate methyltransferase activity.We have reconstituted this pathway in vitro using the native H3K4-specific methyltransferase complex Set1C purified from the fission yeast Schizosaccharomyces pombe and chromatin substrates that contain semi-synthetic H2Bub1.We found that the activity of S. pombe Set1C toward nucleosomal histone H3 is directly enhanced by H2Bub1 in vitro.Importantly, Set1C purified from cells lacking H2Bub1 retained activity on free histone substrates, suggesting that the Set1C remained intact in the absence of H2Bub1.Chromatin immunoprecipitation assays revealed a defect in recruitment of intact Set1C to transcribed chromatin in H2Bub1-deficient mutants.Our data argue that trans-histone crosstalk in S. pombe involves direct enhancement of Set1C methyltransferase activity by H2Bub1, and suggest that this represents a conserved aspect of H2Bub1-H3K4me crosstalk in eukaryotes.
