Institute of Molecular Genetics of Montpellier (IGMM), Centre National de Recherche Scientifique (CNRS), Montpellier, France.
University of Montpellier (UM), Montpellier, France.
Biochem Soc Trans. 2021 Aug 27;49(4):1867-1879. doi: 10.1042/BST20210758.
Different classes of non-coding RNA (ncRNA) influence the organization of chromatin. Imprinted gene domains constitute a paradigm for exploring functional long ncRNAs (lncRNAs). Almost all express an lncRNA in a parent-of-origin dependent manner. The mono-allelic expression of these lncRNAs represses close by and distant protein-coding genes, through diverse mechanisms. Some control genes on other chromosomes as well. Interestingly, several imprinted chromosomal domains show a developmentally regulated, chromatin-based mechanism of imprinting with apparent similarities to X-chromosome inactivation. At these domains, the mono-allelic lncRNAs show a relatively stable, focal accumulation in cis. This facilitates the recruitment of Polycomb repressive complexes, lysine methyltranferases and other nuclear proteins - in part through direct RNA-protein interactions. Recent chromosome conformation capture and microscopy studies indicate that the focal aggregation of lncRNA and interacting proteins could play an architectural role as well, and correlates with close positioning of target genes. Higher-order chromatin structure is strongly influenced by CTCF/cohesin complexes, whose allelic association patterns and actions may be influenced by lncRNAs as well. Here, we review the gene-repressive roles of imprinted non-coding RNAs, particularly of lncRNAs, and discuss emerging links with chromatin architecture.
不同类别的非编码 RNA（ncRNA）影响染色质的组织。印迹基因区域构成了探索功能长 ncRNA（lncRNA）的范例。几乎所有印迹基因都以亲本来源依赖的方式表达一种 lncRNA。这些 lncRNA 的单等位基因表达通过多种机制抑制附近和远处的蛋白质编码基因。有些还控制其他染色体上的基因。有趣的是，几个印迹染色体区域表现出一种发育调控的、基于染色质的印迹机制，与 X 染色体失活具有明显的相似性。在这些区域，单等位基因的 lncRNA 在顺式中表现出相对稳定的、焦点聚集。这有利于多梳抑制复合物、赖氨酸甲基转移酶和其他核蛋白的募集——部分通过直接的 RNA-蛋白质相互作用。最近的染色体构象捕获和显微镜研究表明，lncRNA 和相互作用蛋白的焦点聚集也可能发挥结构作用，并与靶基因的紧密定位相关。高级染色质结构受 CTCF/黏合复合物的强烈影响，其等位基因关联模式和作用也可能受到 lncRNA 的影响。在这里，我们综述了印迹非编码 RNA（尤其是 lncRNA）的基因抑制作用，并讨论了与染色质结构的新联系。
