Mitotic Bookmarking and Chromosomal Coating by Nuclear Receptors: Segregating Myth & Reality

Traditionally viewed as a transcriptionally inert phase, mitosis is now recognized as a critical window during which cells preserve their transcriptional memory. This is executed through selective retention of regulatory proteins on the condensed mitotic chromatin. Two distinct but overlapping mechanisms of mitotic bookmarking and chromosomal coating are proposed to facilitate the faithful transmission of cellular traits and phenotypes across multiple cell divisions. However, their mechanistic boundaries and physiological relevance remain debated. We propose that ‘chromosomal coating’ represents a genome‐wide, non‐sequence‐specific scanning mechanism that increases the probability for ‘mitotic bookmarking’, the site‐specific, functional retention of factors at regulatory elements in the chromatin. The current review explores these mechanisms with a specific focus on nuclear receptors (NRs), a family of ligand‐modulated transcription factors (TFs) central to development, metabolism, and endocrine regulation. Emerging evidence suggests that NRs associate with mitotic chromatin exhibiting the bookmarking phenomenon and also participate in broader receptor‐chromatin interactions via chromosomal coating during mitosis. We also use FOXA1 to draw parallels with nuclear receptors, emphasizing how similar principles may underlie other TF‐mediated chromosomal coating and bookmarking events. By integrating current findings from genomics, imaging‐based approaches, and chromatin profiling techniques, we aim to segregate myth from reality in the context of NR‐chromatin interactions and discuss implications for gene regulation and endocrine‐related pathologies.