全球 RNA-染色质接触图谱揭示了 ncRNA-基因相互作用的以邻近性为主导的连通性模型。

Global mapping of RNA-chromatin contacts reveals a proximity-dominated connectivity model for ncRNA-gene interactions.

机构信息

Department of Biochemistry, Stanford University, Stanford, California, USA.

Department of Chemical and Systems Biology, Stanford University, Stanford, California, USA.

出版信息

Nat Commun. 2023 Sep 28;14(1):6073. doi: 10.1038/s41467-023-41848-9.

Non-coding RNAs (ncRNAs) are transcribed throughout the genome and provide regulatory inputs to gene expression through their interaction with chromatin. Yet, the genomic targets and functions of most ncRNAs are unknown. Here we use chromatin-associated RNA sequencing (ChAR-seq) to map the global network of ncRNA interactions with chromatin in human embryonic stem cells and the dynamic changes in interactions during differentiation into definitive endoderm. We uncover general principles governing the organization of the RNA-chromatin interactome, demonstrating that nearly all ncRNAs exclusively interact with genes in close three-dimensional proximity to their locus and provide a model predicting the interactome. We uncover RNAs that interact with many loci across the genome and unveil thousands of unannotated RNAs that dynamically interact with chromatin. By relating the dynamics of the interactome to changes in gene expression, we demonstrate that activation or repression of individual genes is unlikely to be controlled by a single ncRNA.

非编码 RNA（ncRNAs）在整个基因组中被转录，并通过与染色质的相互作用为基因表达提供调控输入。然而，大多数 ncRNAs 的基因组靶标和功能尚不清楚。在这里，我们使用染色质相关 RNA 测序（ChAR-seq）来绘制人类胚胎干细胞中 ncRNA 与染色质相互作用的全局网络，以及在向确定内胚层分化过程中相互作用的动态变化。我们揭示了支配 RNA-染色质相互作用组组织的一般原则，证明几乎所有的 ncRNA 仅与它们基因座附近的基因进行三维特异性相互作用，并提供了一个预测相互作用组的模型。我们发现了与基因组中许多基因座相互作用的 RNA，并揭示了数千个与染色质动态相互作用的未经注释的 RNA。通过将相互作用组的动态与基因表达的变化相关联，我们证明单个基因的激活或抑制不太可能由单个 ncRNA 控制。