GSE183065
Stable inheritance of H3.3-containing nucleosomes during mitotic cell divisions
It is known that newly synthesized H3.1/H3.2 and H3.3 histones, differing by four or five amino acids, are assembled into nucleosomes via replication-coupled and replication-independent pathways, respectively. However, it is not clear how parental H3.3 is transferred following DNA replication, especially when compared to H3.1. Here, we show that parental H3.3, like H3.1, are stably transferred into daughter cells. Moreover, Mcm2, Pole3 and Pole4, proteins known to engage in parental histone transfer based upon analysis of parental histone modifications, participate in the transfer of H3.3 following DNA replication. Lastly, we found that Mcm2, Pole3 and Pole4 mutants defective in parental histone transfer show defects in chromosome segregations. We propose that parental H3.3 is also stably transferred into daughter cells, contributing to the epigenetic memory of gene expression and the maintenance of genome stability. Overall design: The CUT&TAG and eSPAN experiments were conducted in WT, Mcm2-2A mutant, Pole3 KO and Pole4 KO mES cells. The histone markers performed by CUT&TAG and eSPAN methods in mES cells included H3.3 and H3K36me3.  For the regulation of gene expression, we performed total RNA-seq experiments in WT, Mcm2-2A mutant, Pole3 KO and Pole4 KO mES cells.