TASOR is a pseudo-PARP that directs HUSH complex assembly and epigenetic transposon control.
TASOR is a pseudo-PARP that directs HUSH complex assembly and epigenetic transposon control.
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TASOR是指导HUSH复合物组装和表观遗传转座子控制的假PARP。
DOI：
10.1038/s41467-020-18761-6
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发表时间：
2020-10-02
影响因子：
16.6
通讯作者：
Modis Y
中科院分区：
文献类型：
--
作者：
Douse CH;Tchasovnikarova IA;Timms RT;Protasio AV;Seczynska M;Prigozhin DM;Albecka A;Wagstaff J;Williamson JC;Freund SMV;Lehner PJ;Modis Y
HUSH复合体抑制逆转录病毒、转座子和基因以维持脊椎动物基因组的完整性。HUSH调节表观遗传标记H3 K9 me 3的沉积，但其三个核心亚基- TASOR，MPP 8和Periphilin -如何有助于组装和靶向复合物仍然未知。在这里，我们定义了HUSH组装的生化基础，并发现其模块化结构类似于酵母RNA诱导的转录沉默复合物。TASOR，中央HUSH亚基，与RNA加工组分相关。TASOR是转录基因中LINE-1重复序列和重复外显子上H3 K9 me 3沉积所必需的。在先前研究的背景下，这表明RNA中间体对HUSH活性很重要。我们剖析了转基因抑制所必需的TASOR和MPP 8结构域。结构-功能分析显示TASOR具有靶向H3 K9 me 3沉积所必需的催化失活的PARP结构域。我们的结论是，TASOR是一个多功能的假PARP，指导HUSH组装和表观遗传调控的重复基因组靶点。HUSH复合物在控制病毒和转座因子的转录中起关键作用。在这里，作者定义了HUSH组装的生物化学基础，并表明TASOR亚基含有对HUSH依赖性转基因抑制和H3 K9 me 3在靶基因组范围内沉积至关重要的假PARP结构域。
The HUSH complex represses retroviruses, transposons and genes to maintain the integrity of vertebrate genomes. HUSH regulates deposition of the epigenetic mark H3K9me3, but how its three core subunits — TASOR, MPP8 and Periphilin — contribute to assembly and targeting of the complex remains unknown. Here, we define the biochemical basis of HUSH assembly and find that its modular architecture resembles the yeast RNA-induced transcriptional silencing complex. TASOR, the central HUSH subunit, associates with RNA processing components. TASOR is required for H3K9me3 deposition over LINE-1 repeats and repetitive exons in transcribed genes. In the context of previous studies, this suggests that an RNA intermediate is important for HUSH activity. We dissect the TASOR and MPP8 domains necessary for transgene repression. Structure-function analyses reveal TASOR bears a catalytically-inactive PARP domain necessary for targeted H3K9me3 deposition. We conclude that TASOR is a multifunctional pseudo-PARP that directs HUSH assembly and epigenetic regulation of repetitive genomic targets. The HUSH complex plays a key role in controlling transcription of viruses and transposable elements. Here, the authors define the biochemical basis of HUSH assembly and show that the TASOR subunit contains a pseudo-PARP domain critical for HUSH-dependent transgene repression and H3K9me3 deposition over targets genome wide.
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DOI：
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发表时间：
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影响因子：
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