組蛋白H3第四位賴氨酸的甲基化(H3K4me)對真核生物轉(zhuǎn)錄活性的染色體的形成是至關(guān)重要的。
組蛋白H2B單泛素化(H2Bub1)是另一個與轉(zhuǎn)錄有關(guān)的組蛋白修飾,。研究發(fā)現(xiàn),，在酵母、果蠅以及一些人類細胞系,，H3K4me通過H2Bub1被全面的刺激,。
目前，這些反式的組蛋白修飾通路的機制還不明確,，但是對不同的實驗系統(tǒng)進行的研究表明,，H2Bub1能夠影響甲基轉(zhuǎn)移酶復(fù)合體的亞基構(gòu)成或是直接激活甲基轉(zhuǎn)移酶的活性。
來自加拿大麥吉爾大學(xué)的研究人員已經(jīng)在體外重新構(gòu)建了這個通路,，他們使用來自裂殖酵母的H3K4特異性甲基轉(zhuǎn)移酶復(fù)合體Set1C,，以及含有半合成的H2Bub1的染色質(zhì)底物。
實驗結(jié)果發(fā)現(xiàn),，在體外裂殖酵母的Set1C對核小體組蛋白H3的活性通過H2Bub1被直接增強,。
重要的是，來源于缺失H2Bub1細胞的Set1C保留了對自由的組蛋白底物的活性,，這表明在沒有H2Bub1時Set1C保持完好,。
染色質(zhì)免疫沉淀分析顯示，在H2Bub1缺陷的突變體,，招募完好的Set1C到轉(zhuǎn)錄的染色質(zhì)的過程也是缺陷的,。
該實驗討論了裂殖酵母組蛋白竄擾（crosstalk）與Set1C甲基化轉(zhuǎn)移酶活性通過H2Bub1的作用直接增強的關(guān)系，表明H2Bub1-H3K4me竄擾在真核生物中是保守的,。相關(guān)論文發(fā)表在4月13日的Journal of Biological Chemistry,。（生物谷Deepblue編譯）
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.
