State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences and College of Life Sciences, Nankai University, Tianjin 300071, China.
Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Stem Cell Reports. 2020 Mar 10;14(3):493-505. doi: 10.1016/j.stemcr.2020.02.002.
Both 3D chromatin architecture and long non-coding RNAs (lncRNAs) play essential roles in pluripotency maintenance. However, whether lncRNAs are involved in organizing 3D chromatin structure remains largely unexplored. We identified 39 lncRNAs bound by Klf4, among which we further revealed the 5430416N02Rik promoter is a chromatin interaction hub. Knockout of the 5430416N02Rik locus reduces the proliferation rate of embryonic stem cells (ESCs). Moreover, deleting both the promoter and the gene body of 5430416N02Rik causes a more severe proliferation defect and has a more profound impact on the transcriptome than deleting the gene body alone. The reduced proliferation of the 5430416N02Rik locus knockout ESCs is mainly due to the downregulation of Mid1, the expression of which requires the inter-chromosomal interaction between Mid1 and 5430416N02Rik loci. In summary, our data demonstrated that the lncRNA 5430416N02Rik gene locus maintains the fast proliferation of ESCs by activating the expression of Mid1 through chromatin interaction.
三维染色质结构和长链非编码 RNA（lncRNA）在维持多能性方面都起着至关重要的作用。然而，lncRNA 是否参与组织三维染色质结构在很大程度上仍未被探索。我们鉴定了 39 个被 Klf4 结合的 lncRNA，其中我们进一步揭示了 5430416N02Rik 启动子是一个染色质相互作用枢纽。敲除 5430416N02Rik 基因座会降低胚胎干细胞（ESCs）的增殖率。此外，与单独敲除基因体相比，敲除 5430416N02Rik 的启动子和基因体导致更严重的增殖缺陷，对转录组的影响也更大。5430416N02Rik 基因座敲除 ESC 的增殖减少主要是由于 Mid1 的下调，其表达需要 Mid1 和 5430416N02Rik 基因座之间的染色体间相互作用。总之，我们的数据表明，lncRNA 5430416N02Rik 基因座通过染色质相互作用激活 Mid1 的表达，从而维持 ESC 的快速增殖。
