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首页 » 表观遗传学 » PNAS:表观遗传调控因子JMJ703在调控反转座子活性中的重要作用

PNAS:表观遗传调控因子JMJ703在调控反转座子活性中的重要作用

来源:遗传与发育生物学研究所 2013-01-20 08:59

转座元件是指在基因组中能够移动或复制并重新整合到基因组新位点的DNA片段,它们对动植物基因组的组成、进化和基因表达具有重要影响。而在宿主基因组中,如果失去对转座元件的有效抑制,这些元件将对基因表达和基因组的稳定性构成影响。水稻是主要的粮食作物同时也是重要的单子叶模式植物,其中存在着大量的转座元件,迄今为止,对于水稻宿主基因组如何调节这些转座元件还知之甚少。中科院遗传发育所曹晓风课题组及其合作者以水稻为材料,结合生化分析、全基因组染色质免疫共沉淀分析及转录组学和分子生物学等研究手段,揭示了JMJ703这一表观遗传调控因子在调控反转座子活性中的重要作用。

利用细胞与生化分析,研究者发现JMJ703蛋白是水稻特异的组蛋白H3K4me3/2/1去甲基化酶,它能调节non-LTR类型反转座子Karma及其N端缺失形式LINE1 的转座活性。在jmj703突变体中,H3K4me3激活修饰的升高、DNA甲基化抑制降低,造成了Karma 转录升高和转座激活。前期该课题组研究发现组蛋白H3K9甲基转移酶SDG714参与LTR类型反转座子Tos17的转座,但在jmj703突变体中,Tos17并未发生转座, Tos17位点的表观遗传修饰也未发生改变,说明Tos17不是JMJ703的靶标。为何水稻中不同的组蛋白修饰分别调控Karma和Tos17这两类反转座子?研究者进一步分析发现,Karma和LINE1分别处于不同染色体上H3K4me3 较低的异染色质区,而Tos17位于常染色质区域。研究者提出水稻基因组对待不同染色质微环境的转座元件采用不同的表观遗传修饰,从而持续维持其沉默状态,最终达到稳定基因组的目的。

水稻H3K4去甲基化酶对于转座子的调控有重要作用。值得注意的是,人类多种疾病的发生与一类LINE元件的转座相关。而人类染色体核型与水稻存在着相似性,即异染色质在整个染色体上的散在分布,暗示着人类转座元件的调控可能存在类似的机制,该项工作揭示了主动去除表观遗传激活修饰与反转座子沉默之间的内在联系,水稻中的研究对于人类肿瘤发生的机制提供了一个重要线索。

该结果于1月14日在PNAS杂志在线发表。曹晓风课题组的博士研究生崔勰奎为本论文的共同第一作者。该研究得到科技部重大研究计划和国家自然科学基金委项目的资助。(生物谷Bioon.com)

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.

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