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

Abstract

We report that the eukaryotic replicative helicase CMG (Cdc45-MCM-GINS) is required for differential gene expression in cells produced by asymmetric cell divisions in C. elegans. We found that the C. elegans CMG component, PSF-2 GINS2, is necessary for transcriptional upregulation of the pro-apoptotic gene egl-1 BH3-only that occurs in cells programmed to die after they are produced through asymmetric cell divisions. We propose that CMG's histone chaperone activity causes epigenetic changes at the egl-1 locus during replication in mother cells, and that these changes are required for egl-1 upregulation in cells programmed to die. We find that PSF-2 is also required for the divergence of other cell fates during C. elegans development, suggesting that this function is not unique to egl-1 expression. Our work uncovers an unexpected role of CMG in cell fate decisions and an intrinsic mechanism for gene expression plasticity in the context of asymmetric cell division.