GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE240nnn/GSE240606/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE240606GEOGSEfalseMYC and MAX drive the reactivation of the genome after mitosisShortly 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. 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 musculus[42562574]