Long noncoding RNA <i>DREAMer</i> bridges the DREAM complex and E2f1 to regulate endoreplication in <i>Drosophila</i>

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 <i>DREAMer</i>, that bridges the interaction between E2f1 and the dREAM complex to regulate endoreplication specifically in <i>Drosophila</i> salivary gland. We show that E2f1 directly stimulates <i>DREAMer</i> expression, whereas <i>DREAMer</i> mediates the repression of <i>e2f1</i> transcription by modulating the recruitment of the dREAM complex to the <i>e2f1</i> promoter via a direct interaction with the dREAM component E2f2. The depletion of <i>DREAMer</i> impairs dREAM binding, leading to derepression of <i>e2f1</i> transcription, which ultimately increases E2f1 activity and promotes the endoreplication. Furthermore, the transcriptomic analysis revealed profound changes in cell cycle-related gene expression in <i>DREAMer^KO</i> salivary glands. Together, our findings reveal an lncRNA-mediated link between the dREAM complex and E2f1, which regulates endoreplication during development.