轉座元件是指在基因組中能夠移動或復制并重新整合到基因組新位點的DNA片段,它們對動植物基因組的組成、進化和基因表達具有重要影響,。而在宿主基因組中,,如果失去對轉座元件的有效抑制,,這些元件將對基因表達和基因組的穩(wěn)定性構成影響,。水稻是主要的糧食作物同時也是重要的單子葉模式植物,其中存在著大量的轉座元件,,迄今為止,,對于水稻宿主基因組如何調節(jié)這些轉座元件還知之甚少。中科院遺傳發(fā)育所曹曉風課題組及其合作者以水稻為材料,,結合生化分析,、全基因組染色質免疫共沉淀分析及轉錄組學和分子生物學等研究手段,揭示了JMJ703這一表觀遺傳調控因子在調控反轉座子活性中的重要作用,。
利用細胞與生化分析,,研究者發(fā)現(xiàn)JMJ703蛋白是水稻特異的組蛋白H3K4me3/2/1去甲基化酶,它能調節(jié)non-LTR類型反轉座子Karma及其N端缺失形式LINE1 的轉座活性,。在jmj703突變體中,,H3K4me3激活修飾的升高、DNA甲基化抑制降低,,造成了Karma 轉錄升高和轉座激活,。前期該課題組研究發(fā)現(xiàn)組蛋白H3K9甲基轉移酶SDG714參與LTR類型反轉座子Tos17的轉座,但在jmj703突變體中,,Tos17并未發(fā)生轉座,, Tos17位點的表觀遺傳修飾也未發(fā)生改變,說明Tos17不是JMJ703的靶標,。為何水稻中不同的組蛋白修飾分別調控Karma和Tos17這兩類反轉座子,?研究者進一步分析發(fā)現(xiàn),Karma和LINE1分別處于不同染色體上H3K4me3 較低的異染色質區(qū),,而Tos17位于常染色質區(qū)域,。研究者提出水稻基因組對待不同染色質微環(huán)境的轉座元件采用不同的表觀遺傳修飾,從而持續(xù)維持其沉默狀態(tài),最終達到穩(wěn)定基因組的目的,。
水稻H3K4去甲基化酶對于轉座子的調控有重要作用,。值得注意的是,人類多種疾病的發(fā)生與一類LINE元件的轉座相關,。而人類染色體核型與水稻存在著相似性,,即異染色質在整個染色體上的散在分布,暗示著人類轉座元件的調控可能存在類似的機制,,該項工作揭示了主動去除表觀遺傳激活修飾與反轉座子沉默之間的內在聯(lián)系,,水稻中的研究對于人類腫瘤發(fā)生的機制提供了一個重要線索,。
該結果于1月14日在PNAS雜志在線發(fā)表,。曹曉風課題組的博士研究生崔勰奎為本論文的共同第一作者。該研究得到科技部重大研究計劃和國家自然科學基金委項目的資助,。(生物谷Bioon.com)
doi: 10.1073/pnas.1217020110
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Control of transposon activity by a histone H3K4 demethylase in rice
Xiekui Cuia,b,1, Ping Jinc,d,1, Xia Cuia, Lianfeng Gua, Zhike Lua, Yongming Xuea,b, Liya Weia,b, Jianfei Qia, Xianwei Songa, Ming Luoe, Gynheung Anc, and Xiaofeng Caoa,2
Transposable elements (TEs) are ubiquitously present in plant genomes and often account for significant fractions of the nuclear DNA. For example, roughly 40% of the rice genome consists of TEs, many of which are retrotransposons, including 14% LTR- and ∼1% non-LTR retrotransposons. Despite their wide distribution and abundance, very few TEs have been found to be transpositional, indicating that TE activities may be tightly controlled by the host genome to minimize the potentially mutagenic effects associated with active transposition. Consistent with this notion, a growing body of evidence suggests that epigenetic silencing pathways such as DNA methylation, RNA interference, and H3K9me2 function collectively to repress TE activity at the transcriptional and posttranscriptional levels. It is not yet clear, however, whether the removal of histone modifications associated with active transcription is also involved in TE silencing. Here, we show that the rice protein JMJ703 is an active H3K4-specific demethylase required for TEs silencing. Impaired JMJ703 activity led to elevated levels of H3K4me3, the misregulation of numerous endogenous genes, and the transpositional reactivation of two families of non-LTR retrotransposons. Interestingly, loss of JMJ703 did not affect TEs (such as Tos17) previously found to be silenced by other epigenetic pathways. These results indicate that the removal of active histone modifications is involved in TE silencing and that different subsets of TEs may be regulated by distinct epigenetic pathways.