Dynamics and regulation of mitotic chromatin accessibility bookmarking at single-cell resolution

Although mitotic chromosomes are highly compacted and transcriptionally inert, some active chromatin features are retained during mitosis to ensure the proper postmitotic reestablishment of maternal transcriptional programs, a phenomenon termed mitotic bookmarking. However, the dynamics and regulation of mitotic bookmarking have not been systemically surveyed. Using single-cell transposase-accessible chromatin sequencing (scATAC-seq), we examined 6538 mitotic L02 human liver cells of variable stages and found that chromatin accessibility remained changing throughout cell division, with a constant decrease until metaphase and a gradual increase as chromosomes segregated. In particular, a subset of chromatin regions were identified to remain open throughout mitosis, and genes associated with these bookmarked regions are primarily linked to rapid reactivation upon mitotic exit. We also demonstrated that nuclear transcription factor Y subunit alpha (NF-YA) preferentially occupied bookmarked regions and contributed to transcriptional reactivation after mitosis. Our study uncovers the dynamic and regulatory blueprint of mitotic bookmarking.

Automated summary

Although mitotic chromosomes are highly compacted and transcriptionally inert, some active chromatin features are retained during mitosis, referred to as mitotic bookmarking, to ensure proper postmitotic reestablishment of maternal transcriptional programs. Using single-cell transposase-accessible chromatin sequencing (scATAC-seq), this study found that chromatin accessibility changes throughout cell division, with a constant decrease until metaphase and a gradual increase as chromosomes segregate. Certain chromatin regions remain open throughout mitosis, and genes associated with these bookmarked regions are quickly reactivated upon mitotic exit. The nuclear transcription factor Y subunit alpha (NF-YA) plays a role in transcriptional reactivation after mitosis.