A dynamic role for transcription factors in restoring transcription through mitosis

Mitosis involves intricate steps, such as DNA condensation, nuclear membrane disassembly, and phosphorylation cascades that temporarily halt gene transcription. Despite this disruption, daughter cells remarkably retain the parent cell's gene expression pattern, allowing for efficient transcriptional memory after division. Early studies in mammalian cells suggested that transcription factors (TFs) mark genes for swift reactivation, a phenomenon termed 'mitotic bookmarking', but conflicting data emerged regarding TF presence on mitotic chromosomes. Recent advancements in live-cell imaging and fixation-free genomics challenge the conventional belief in universal formaldehyde fixation, revealing dynamic TF interactions during mitosis. Here, we review recent studies that provide examples of at least four modes of TF-DNA interaction during mitosis and the molecular mechanisms that govern these interactions. Additionally, we explore the impact of these interactions on transcription initiation post-mitosis. Taken together, these recent studies call for a paradigm shift toward a dynamic model of TF behavior during mitosis, underscoring the need for incorporating dynamics in mechanistic models for re-establishing transcription post-mitosis.