School of Medicine, Nantong University, Nantong 226001, China.
College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
Sci Adv. 2024 Nov 8;10(45):eadr4936. doi: 10.1126/sciadv.adr4936.
Rb/E2f and DREAM complexes play vital roles in regulating cell cycle progression. To date, how they coordinate their functions to regulate cell cycle-dependent gene expression is not clear. Here, we identified a long noncoding RNA (lncRNA), which we named , that bridges the interaction between E2f1 and the dREAM complex to regulate endoreplication specifically in salivary gland. We show that E2f1 directly stimulates expression, whereas mediates the repression of transcription by modulating the recruitment of the dREAM complex to the promoter via a direct interaction with the dREAM component E2f2. The depletion of impairs dREAM binding, leading to derepression of transcription, which ultimately increases E2f1 activity and promotes the endoreplication. Furthermore, the transcriptomic analysis revealed profound changes in cell cycle-related gene expression in salivary glands. Together, our findings reveal an lncRNA-mediated link between the dREAM complex and E2f1, which regulates endoreplication during development.
Rb/E2f 和 DREAM 复合物在调节细胞周期进程中发挥着重要作用。迄今为止，它们如何协调其功能来调节细胞周期依赖性基因表达还不清楚。在这里，我们鉴定了一个长非编码 RNA（lncRNA），我们将其命名为 ，它连接了 E2f1 和 dREAM 复合物之间的相互作用，以专门在唾液腺中调节内复制。我们表明，E2f1 直接刺激 的表达，而 通过调节 dREAM 复合物到 的募集来介导 的转录抑制，通过与 dREAM 成分 E2f2 的直接相互作用。 的耗竭会损害 dREAM 结合，导致 的转录去抑制，这最终增加了 E2f1 的活性并促进了内复制。此外，转录组分析显示唾液腺中细胞周期相关基因表达发生了深刻变化。总之，我们的发现揭示了 dREAM 复合物和 E2f1 之间的 lncRNA 介导的联系，该联系调节了发育过程中的内复制。
