PDF(Pubmed)
Abstract：
The HUSH complex recognizes and silences foreign DNA such as viruses, transposons, and transgenes without prior exposure to its targets. Here, we show that endogenous targets of the HUSH complex fall into two distinct classes based on the presence or absence of H3K9me3. These classes are further distinguished by their transposon content and differential response to the loss of HUSH. A de novo genomic rearrangement at the Sox2 locus induces a switch from H3K9me3-independent to H3K9me3-associated HUSH targeting, resulting in silencing. We further demonstrate that HUSH interacts with the termination factor WDR82 and-via its component MPP8-with nascent RNA. HUSH accumulates at sites of high RNAPII occupancy including long exons and transcription termination sites in a manner dependent on WDR82 and CPSF. Together, our results uncover the functional diversity of HUSH targets and show that this vertebrate-specific complex exploits evolutionarily ancient transcription termination machinery for co-transcriptional chromatin targeting and genome surveillance.
摘要：
HUSH复合体识别并沉默外源DNA，如病毒，转座子,和没有事先暴露于其靶标的转基因。这里,我们表明，基于H3K9me3的存在或不存在，HUSH复合物的内源性靶标分为两类。这些类别通过它们的转座子含量和对HUSH损失的差异反应进一步区分。Sox2基因座处的从头基因组重排诱导从H3K9me3非依赖性转换为H3K9me3相关的HUSH靶向，导致沉默。我们进一步证明HUSH与终止因子WDR82相互作用，并通过其组分MPP8与新生RNA相互作用。HUSH以依赖于WDR82和CPSF的方式积累在高RNAPII占据位点,包括长外显子和转录终止位点。一起,我们的研究结果揭示了HUSH靶标的功能多样性,并表明这种脊椎动物特异性复合物利用进化上古老的转录终止机制进行共转录染色质靶向和基因组监测.
