Simultaneous mapping of 3D structure and nascent RNAs argues against nuclear compartments that preclude transcription.
Simultaneous mapping of 3D structure and nascent RNAs argues against nuclear compartments that preclude transcription.
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DOI：
10.1016/j.celrep.2022.111730
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发表时间：
2022-11-29
期刊：
影响因子：
8.8
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中科院分区：
文献类型：
--
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哺乳动物基因组被组织成三维DNA结构，称为A/B区室，与转录活性/不活性相关。然而，由于缺乏同时测量DNA组织和转录的方法，这些结构是否仅仅与基因表达相关，或者是否允许/不允许转录，在很大程度上仍然未知。最近，我们开发了RNA & DNA (RD)-SPRITE，它可以对RNA和DNA的空间组织进行全基因组测量。在这里，我们展示了RD-SPRITE测量新生pre- mrna周围的基因组结构并绘制它们的空间联系。我们发现转录发生在B区室内（多个活性基因同时在同一个B区室内共定位）和靠近核仁的基因上。这些结果表明，被认为不活跃的核结构附近或内部的定位并不妨碍转录，并且活性转录可以在整个细胞核中发生。总的来说，我们预计RD-SPRITE将成为探索基因组结构和转录之间关系的有力工具。Goronzy等人利用RD-SPRITE同时绘制3D基因组结构和全基因组新生RNA转录图谱，发现RNA聚合酶II转录可以发生在细胞核的多个区室中，包括先前与非活性转录相关的区域，如B区室和靠近核核的区域。
Mammalian genomes are organized into three-dimensional DNA structures called A/B compartments that are associated with transcriptional activity/inactivity. However, whether these structures are simply correlated with gene expression or are permissive/impermissible to transcription has remained largely unknown because we lack methods to measure DNA organization and transcription simultaneously. Recently, we developed RNA & DNA (RD)-SPRITE, which enables genome-wide measurements of the spatial organization of RNA and DNA. Here we show that RD-SPRITE measures genomic structure surrounding nascent pre-mRNAs and maps their spatial contacts. We find that transcription occurs within B compartments—with multiple active genes simultaneously colocalizing within the same B compartment—and at genes proximal to nucleoli. These results suggest that localization near or within nuclear structures thought to be inactive does not preclude transcription and that active transcription can occur throughout the nucleus. In general, we anticipate RD-SPRITE will be a powerful tool for exploring relationships between genome structure and transcription. Using RD-SPRITE to simultaneously map 3D genome structure and nascent RNA transcription genome-wide, Goronzy et al. find that RNA polymerase II transcription can occur within multiple compartments in the nucleus, including regions previously associated with inactive transcription, such as the B compartment and close to the nucleolus.
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