Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria.
Cell. 2012 Nov 21;151(5):964-80. doi: 10.1016/j.cell.2012.10.040. Epub 2012 Nov 15.
Eukaryotic genomes are colonized by transposons whose uncontrolled activity causes genomic instability. The piRNA pathway silences transposons in animal gonads, yet how this is achieved molecularly remains controversial. Here, we show that the HMG protein Maelstrom is essential for Piwi-mediated silencing in Drosophila. Genome-wide assays revealed highly correlated changes in RNA polymerase II recruitment, nascent RNA output, and steady-state RNA levels of transposons upon loss of Piwi or Maelstrom. Our data demonstrate piRNA-mediated trans-silencing of hundreds of transposon copies at the transcriptional level. We show that Piwi is required to establish heterochromatic H3K9me3 marks on transposons and their genomic surroundings. In contrast, loss of Maelstrom affects transposon H3K9me3 patterns only mildly yet leads to increased heterochromatin spreading, suggesting that Maelstrom acts downstream of or in parallel to H3K9me3. Our work illustrates the widespread influence of transposons and the piRNA pathway on chromatin patterns and gene expression.
真核生物基因组被转座子所占据，而这些转座子的不受控制的活动会导致基因组不稳定。piRNA 途径在动物性腺中沉默转座子，但这在分子水平上是如何实现的仍存在争议。在这里，我们表明 HMG 蛋白 Maelstrom 对于果蝇中 Piwi 介导的沉默是必需的。全基因组分析显示，在 Piwi 或 Maelstrom 缺失时，RNA 聚合酶 II 的募集、新生 RNA 的输出和转座子的稳态 RNA 水平都发生了高度相关的变化。我们的数据表明，piRNA 介导了数百个转座子拷贝在转录水平上的跨沉默。我们表明，Piwi 被需要在转座子及其基因组周围建立异染色质 H3K9me3 标记。相比之下，Maelstrom 的缺失仅对转座子的 H3K9me3 模式产生轻微影响，但会导致异染色质扩散增加，表明 Maelstrom 作用于 H3K9me3 之后或与之平行。我们的工作说明了转座子和 piRNA 途径对染色质模式和基因表达的广泛影响。
