MYC and MAX drive the reactivation of the genome after mitosis

While recent work has illuminated how specific groups of genes are reactivated, whether dedicated mechanisms enable the global, efficient and accurate post-mitotic reactivation of the genome remains unknown. Here, we show that the MYC/MAX transcription factors drive post-mitotic genome reactivation in ES cells.

Although MYC undergoes extensive phosphorylation and dissociates from chromatin during mitosis, MAX maintains DNA binding capacity and acts as a mitotic bookmarking factor. Combining pharmacological inhibition of MYC/MAX, inducible genetic MAX ablation, mitotic arrest-release assays and cell cycle-resolved single-cell transcriptomics, we establish the indispensable role of MYC/MAX in post-mitotic hyper-transcription. Our findings suggest a novel mitotic bookmarking function for MAX that orchestrates MYC recruitment to foster post-mitotic transcription.