Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; RNA Discovery Center, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Mechanistic, Interdisciplinary Studies of Biological Systems, University of North Carolina, Chapel Hill, NC 27599, USA.
Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
Cell Rep. 2023 Jul 25;42(7):112803. doi: 10.1016/j.celrep.2023.112803. Epub 2023 Jul 11.
During mouse embryogenesis, expression of the long non-coding RNA (lncRNA) Airn leads to gene repression and recruitment of Polycomb repressive complexes (PRCs) to varying extents over a 15-Mb domain. The mechanisms remain unclear. Using high-resolution approaches, we show in mouse trophoblast stem cells that Airn expression induces long-range changes to chromatin architecture that coincide with PRC-directed modifications and center around CpG island promoters that contact the Airn locus even in the absence of Airn expression. Intensity of contact between the Airn lncRNA and chromatin correlated with underlying intensity of PRC recruitment and PRC-directed modifications. Deletion of CpG islands that contact the Airn locus altered long-distance repression and PRC activity in a manner that correlated with changes in chromatin architecture. Our data imply that the extent to which Airn expression recruits PRCs to chromatin is controlled by DNA regulatory elements that modulate proximity of the Airn lncRNA product to its target DNA.
在小鼠胚胎发生过程中，长非编码 RNA（lncRNA）Airn 的表达导致基因抑制，并在 15-Mb 区域内以不同程度募集多梳抑制复合物（PRC）。其机制尚不清楚。使用高分辨率方法，我们在小鼠滋养层干细胞中表明，Airn 表达诱导染色质结构的远程变化，与 PRC 导向的修饰一致，并且集中在 CpG 岛启动子周围，即使在没有 Airn 表达的情况下，CpG 岛启动子也与 Airn 基因座接触。Airn lncRNA 与染色质之间的接触强度与 PRC 募集和 PRC 导向的修饰的基础强度相关。与 Airn 基因座接触的 CpG 岛缺失改变了长距离抑制和 PRC 活性，其方式与染色质结构的变化相关。我们的数据表明，Airn 表达募集 PRC 到染色质的程度受 DNA 调节元件控制，这些调节元件调节 Airn lncRNA 产物与其靶 DNA 的接近程度。
