H3S10-phosphorylation spreading in mitosis stably preserves 3D chromatin structure and functions

Gene regulatory landscape of a cell is faithfully recapitulated in daughter cell despite widespread loss of epigenetic marks, transcription and 3D chromatin structure during cell division. How a cell remembers its gene regulatory landscape through mitosis is poorly understood. Recently, a histone modification that spreads on chromatin was postulated to be a preserver of chromatin state. Unlike most histone modifications, mitotic cells gain H3S10p but its mitotic bookmarking roles are unknown. Here, we show that as the cell loses its interphase-specific chromatin structure, spreading of H3S10p occurs throughout active chromatin domains. The level of spreading is proportional to the activity of a domain. H3S10pmarked chromatin domains are formed earlier post mitosis. Further, within the domains, promoters but not enhancers are hyper-marked by H3S10p. Using mitosis specific expression of H3S10 and its mutants (H3S10A and H3S10D), we reveal that the loss of mitotic H3S10p causes widespread opening of promoters, resulting in abrupt transcription in the next interphase. We propose that H3S10p spreading preserves the 3D-chromatin epigenetic memory where it acts as a rheostat to fine-tune gene transcription in recently divided cells.