Fig. 6: Schematic model how E2Fs and RBR induce developmental quiescence.

a Canonical E2Fs function as co-repressors of cell cycle genes with RBR. Left: in the wild-type, E2Fs form complexes with RBR to repress cell cycle genes and allow cell division arrest in quiescent and differentiated cells. Middle: in the e2fabc mutant, lack of RBR-E2F complexes results in de-repression of cell cycle genes leading to a delay in cell differentiation as well as division reactivation in quiescent cells. Right: in RBR-deficient lines, E2F/RBR complexes are also lacking, but E2Fs are fully active, leading to a more pronounced hyperactivation of cell cycle genes and thus completely preventing cell differentiation, and inducing cell death. b Distinct molecular roles of E2Fs and MYB3Rs in the control of cell cycle arrest. Top: in the wild-type, Repressor complexes containing RBR, E2Fs and MYB3Rs target G1/S and G2/M genes to repress their expression either via the MSA or the E2F motifs. Middle: in the myb3r1,3,5 mutant that lacks repressor MYB3Rs, E2Fs are still present and able to repress G1/S and some G2/M genes bound via the E2F motif. Cell proliferation is therefore not induced in differentiated cells. Bottom: in the e2fabc mutant, repressor MYB3Rs can still repress some G2/M genes with or without RBR, but repression of both G1/S and G2/M activators such as MYB3R4 is lost, resulting in enhanced cell proliferation. Model was created by using Biorender.