Mitotic MAX bookmarking drives MYC-dependent hypertranscription at TBP-bound promoters

Faithful genome reactivation after mitosis is essential for cell identity, yet the mechanisms driving global postmitotic transcription remain unclear. Here, we show that the MYC oncogene and its obligate partner MAX drive a postmitotic hypertranscriptional state in mouse embryonic stem cells. Cell cycle–resolved single-cell RNA-seq in inducible Max −/− cells reveals that early G1 hypertranscription is strongly impaired without MAX. Mechanistically, MAX remains bound to thousands of promoters during mitosis, while MYC is largely excluded. Using high-temporal-resolution profiling, pharmacological inhibition of MYC/MAX, and acute MAX degradation at mitotic exit, we demonstrate that MAX mitotic binding triggers rapid MYC recruitment and transcriptional amplification of TBP-bound promoters by enhancing RNA polymerase II occupancy and efficient initiation and elongation. These findings redefine MYC/MAX as master regulators of gene regulatory inheritance across mitosis.