Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi

Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi
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DOI:
10.1126/science.1074973
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发表时间:
2002-09-13
期刊:
影响因子:
56.9
通讯作者:
Martienssen, RA
Martienssen, RA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Volpe, TA;Kidner, C;Martienssen, RA

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真核异染色质的特征在于高密度的重复序列和转座子,以及修饰的组蛋白,并且影响基因表达和染色体分离。在裂殖酵母裂殖酵母中,我们删除了argonaute、dicer和RNA依赖性RNA聚合酶基因同源物,这些基因编码负责RNA干扰(RNAi)的部分机制。缺失导致着丝粒异染色质重复序列的互补转录本异常积累。这伴随着整合在着丝粒处的转基因的转录去抑制、组蛋白H3赖氨酸-9甲基化的丧失和着丝粒功能的损害。我们提出,由着丝粒重复序列产生的双链RNA通过RNAi靶向异染色质的形成和维持。
Eukaryotic heterochromatin is characterized by a high density of repeats and transposons, as well as by modified histones, and influences both gene expression and chromosome segregation. In the fission yeast Schizosaccharomyces pombe, we deleted the argonaute, dicer, and RNA-dependent RNA polymerase gene homologs, which encode part of the machinery responsible for RNA interference (RNAi). Deletion results in the aberrant accumulation of complementary transcripts from centromeric heterochromatic repeats. This is accompanied by transcriptional de-repression of transgenes integrated at the centromere, loss of histone H3 lysine-9 methylation, and impairment of centromere function. We propose that double-stranded RNA arising from centromeric repeats targets formation and maintenance of heterochromatin through RNAi.