The replicative helicase CMG is required for the divergence of cell fates during asymmetric cell division in vivo

The mechanisms that enable differential gene expression in daughter cells produced by asymmetric cell divisions are not well understood. We discovered that the eukaryotic replicative helicase CMG (Cdc45-MCM-GINS) is required for this process in C. elegans. During C. elegans development, some dividing cells give rise to a daughter that survives and a daughter that dies. We found that PSF-2 GINS2, a component of C. elegans CMG, is necessary for the transcriptional burst of the pro-apoptotic gene egl-1 BH3-only, which occurs in the daughter that dies immediately following mother cell division. We present evidence that this requirement is independent of the function of CMG in DNA unwinding. We propose that the recently described histone chaperone activity of CMG causes epigenetic changes at the egl-1 locus during replication in mother cells, and that these changes are required for the increase in egl-1 transcription in the daughter that dies. We also find that PSF-2 is required for the divergence of other cell fates during C. elegans development, suggesting that this function is not restricted to the regulation of egl-1 expression. Our work uncovers a new and unexpected role of CMG in cell fate and a novel intrinsic mechanism for gene expression plasticity in the context of asymmetric cell division.