Intergenic transcripts regulate the epigenetic state of rRNA genes
Intergenic transcripts regulate the epigenetic state of rRNA genes
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DOI：
10.1016/j.molcel.2006.03.028
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发表时间：
2006-05-05
期刊：
影响因子：
16
通讯作者：
Santoro, Raffaella
中科院分区：
文献类型：
--
作者：
Mayer, Christine;Schmitz, Kerstin-Maike;Santoro, Raffaella
来自分离rRNA基因（rDNA）的基因间间隔（IGS）的转录本已经被发现了二十年；然而，它们的生物学作用在很大程度上是未知的。在这里，我们表明IGS转录本是在rDNA阵列子集启动子上建立和维持特定异色结构所必需的。其作用机制似乎是通过染色质重塑复合体NoRC的大亚基TIP5与150-300个核苷酸rna的相互作用介导的，这些rna在序列上与rDNA启动子互补。破坏TIP5 RNA结合的突变损害了NoRC与rDNA的关联，并降低了促进h3k9和h4k20甲基化和HP1募集的作用。IGS转录物的敲低消除了NoRC的核仁定位，降低了DNA甲基化，增强了rDNA转录。研究结果揭示了IGS转录本在rDNA位点的染色质结构和表观遗传控制中的重要作用。
Transcripts originating from the intergenic spacer (IGS) that separates rRNA genes (rDNA) have been known for two decades; their biological role, however, is largely unknown. Here we show that IGS transcripts are required for establishing and maintaining a specific heterochromatic configuration at the promoter of a subset of rDNA arrays. The mechanism of action appears to be mediated through the interaction of TIP5, the large subunit of the chromatin remodeling complex NoRC, with 150-300 nucleotide RNAs that are complementary in sequence to the rDNA promoter. Mutations that abrogate RNA binding of TIP5 impair the association of NoRC with rDNA and fall to promote H3K9&H4K20 methylation and HP1 recruitment. Knockdown of IGS transcripts abolishes the nucleolar localization of NoRC, decreases DNA methylation, and enhances rDNA transcription. The results reveal an important contribution of processed IGS transcripts in chromatin structure and epigenetic control of the rDNA locus.