Institut de recherches cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, QC, H2W 1R7, Canada.
Département de biochimie et médecine moléculaire Université de Montréal, 2900 Boulevard Edouard-Montpetit, Montréal, QC, H3T 1J4, Canada.
Nat Commun. 2020 Apr 14;11(1):1781. doi: 10.1038/s41467-020-15609-x.
Polycomb Group (PcG) proteins form memory of transient transcriptional repression that is necessary for development. In Drosophila, DNA elements termed Polycomb Response Elements (PREs) recruit PcG proteins. How PcG activities are targeted to PREs to maintain repressed states only in appropriate developmental contexts has been difficult to elucidate. PcG complexes modify chromatin, but also interact with both RNA and DNA, and RNA is implicated in PcG targeting and function. Here we show that R-loops form at many PREs in Drosophila embryos, and correlate with repressive states. In vitro, both PRC1 and PRC2 can recognize R-loops and open DNA bubbles. Unexpectedly, we find that PRC2 drives formation of RNA-DNA hybrids, the key component of R-loops, from RNA and dsDNA. Our results identify R-loop formation as a feature of Drosophila PREs that can be recognized by PcG complexes, and RNA-DNA strand exchange as a PRC2 activity that could contribute to R-loop formation.
多梳组（PcG）蛋白形成对发育所必需的瞬时转录抑制的记忆。在果蝇中，称为多梳反应元件（PREs）的 DNA 元件招募 PcG 蛋白。PcG 活性如何靶向 PRE 以仅在适当的发育环境中维持抑制状态一直难以阐明。PcG 复合物修饰染色质，但也与 RNA 和 DNA 相互作用，并且 RNA 与 PcG 靶向和功能有关。在这里，我们表明 R 环在果蝇胚胎中的许多 PRE 中形成，并与抑制状态相关。在体外，PRC1 和 PRC2 都可以识别 R 环并打开 DNA 泡。出乎意料的是，我们发现 PRC2 从 RNA 和 dsDNA 驱动 RNA-DNA 杂交的形成，这是 R 环的关键组成部分。我们的结果表明 R 环的形成是果蝇 PRE 的一个特征，PcG 复合物可以识别，并且 RNA-DNA 链交换是 PRC2 活性，它可以有助于 R 环的形成。
