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MYC and MAX drive the reactivation of the genome after mitosis

ABSTRACT: Shortly after mitosis, a wave of hyper-transcription reactivates the genome, especially in mouse embryonic stem (ES) cells, where rapid reactivation is essential for self-renewal and pluripotency. 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. These findings hold significant implications for medically relevant contexts where cell proliferation is of paramount importance. We anticipate that the study of mitotic bookmarking by MYC/MAX and of the effects of drugs targeting their interaction in such process will be relevant for our understanding of cancer and its treatments.

ORGANISM(S): Mus musculus

PROVIDER: GSE240606 | GEO | 2026/09/28

REPOSITORIES: GEO

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