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bioRxiv · 10.1101/858746

E2F-dependent genetic oscillators control endoreplication

Moon, N. S.·Kim, M.
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Abstract

Polyploidy is an integral part of development and is associated with cellular stress, aging and pathological conditions. The endoreplication cycle, comprised of successive alternations of G and S phases without cell division, is widely employed to produce polyploid cells. The endocycle is driven by continuous oscillations of Cyclin E/Cdk2 activity, which is governed by E2F transcription factors. In this study, we provide mechanistic insight on how E2F-dependent Cdk oscillations during endocycles are maintained in Drosophila salivary glands. Genetic experiments revealed that an alternative splicing isoform of E2F1, E2F1b, regulates the circuitry of timely S phase entry and exit by activating a subset of E2F target genes. E2F1b regulates the Drosophila ortholog of p27CIP/KIP-like Cdk inhibitor Dacapo to precisely time S phase entry by controlling the CycE/Cdk2 activity threshold. Upon entry to S phase, E2F1b-dependent PCNA expression establishes a negative feedback loop through the PIP box-mediated degradation of E2F1. Overall, our study uncovers a network of E2F-dependent genetic oscillators that are critical for the periodic transition between G and S phases during endoreplication.

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Moon, N. S., Kim, M.. 2019-11-29. E2F-dependent genetic oscillators control endoreplication. https://doi.org/10.1101/858746

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