A chromodomain protein mediates heterochromatin-directed piRNA expression
A chromodomain protein mediates heterochromatin-directed piRNA expression
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染色质结构域蛋白介导异染色质定向的 piRNA 表达
DOI：
10.1073/pnas.2103723118
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Xuezhu Feng
中科院分区：
文献类型：
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作者：
Xinya Huang;Peng Cheng;Chenchun Weng;Zongxiu Xu;Chenming Zeng;Xiangyang Chen;Chengming Zhu;Shouhong Guang;Xuezhu Feng
PIWI相互作用RNA（piRNA）在后生动物中高度保守，并起区分自身和非自身核酸、沉默转座因子、防御病毒感染、保护生殖系完整性和介导跨代遗传的作用。皮尔纳源基因座如何被有效地转录还知之甚少。在这项工作中，我们使用正向和反向遗传方法来破译秀丽隐杆线虫种系中皮尔纳转录的分子机制。我们鉴定了一种染色体结构域蛋白UAD-2，其是皮尔纳焦点形成、上游序列转录复合物与皮尔纳基因的关联以及皮尔纳产生所需的。这项工作表明，异染色质皮尔纳基因座的转录依赖于组蛋白标记的读者和核心转录机制的协调招募。PIWI相互作用RNA（piRNA）在抑制转座子、维持基因组完整性和防御病毒感染方面发挥重要作用。皮尔纳源基因座如何被有效地转录还知之甚少。在这里，我们表明，在秀丽隐杆线虫中，皮尔纳簇的转录取决于染色质微环境和含染色体结构域的蛋白质UAD-2。皮尔纳簇在生殖细胞核中形成不同的焦点。我们进行了正向遗传筛选，并鉴定了皮尔纳焦点形成所需的UAD-2。在不存在组蛋白3赖氨酸27甲基化或适当的染色质重塑状态的情况下，UAD-2从皮尔纳焦点耗尽。UAD-2募集上游序列转录复合物（USTC），其将Ruby基序结合到皮尔纳启动子并促进皮尔纳生成。反之亦然，UAD-2需要USTC复合物来与皮尔纳焦点缔合。因此，异染色质小RNA源基因座的转录依赖于组蛋白标记的阅读器和核心转录机制到DNA的协调募集。
Significance PIWI-interacting RNAs (piRNAs) are highly conserved among metazoan and act to distinguish self and nonself nucleic acids, silence transposable elements, defend against viral infections, protect germline integrity, and mediate transgenerational inheritance. How piRNA source loci are efficiently transcribed is poorly understood. In this work, we used both forward and reverse genetic approaches to decipher the molecular mechanisms of piRNA transcription in the Caenorhabditis elegans germline. We identified a chromodomain protein, UAD-2, that is required for piRNA focus formation, the association of an upstream sequence transcription complex with the piRNA genes, and piRNA production. This work suggested that transcription of heterochromatic piRNA loci relies on coordinated recruitment of both the readers of histone marks and the core transcriptional machinery. PIWI-interacting RNAs (piRNAs) play significant roles in suppressing transposons, maintaining genome integrity, and defending against viral infections. How piRNA source loci are efficiently transcribed is poorly understood. Here, we show that in Caenorhabditis elegans, transcription of piRNA clusters depends on the chromatin microenvironment and a chromodomain-containing protein, UAD-2. piRNA clusters form distinct focus in germline nuclei. We conducted a forward genetic screening and identified UAD-2 that is required for piRNA focus formation. In the absence of histone 3 lysine 27 methylation or proper chromatin-remodeling status, UAD-2 is depleted from the piRNA focus. UAD-2 recruits the upstream sequence transcription complex (USTC), which binds the Ruby motif to piRNA promoters and promotes piRNA generation. Vice versa, the USTC complex is required for UAD-2 to associate with the piRNA focus. Thus, transcription of heterochromatic small RNA source loci relies on coordinated recruitment of both the readers of histone marks and the core transcriptional machinery to DNA.