Gamete fusion rapidly reconstitutes a bi-partite transcription factor to block re-fertilization
The ploidy cycle, integral to sexual reproduction, requires not only meiosis to halve the number of chromosomes, but also mechanisms that ensure zygotes are formed by exactly two partners1-5. During sexual reproduction of the fungal model organism Schizosaccharomyces pombe, haploid P- and M-cells normally fuse to form a diploid zygote that immediately enters meiosis6. Here, we reveal that fast post-fusion reconstitution of a bi-partite transcription factor actively blocks re-fertilization. We first identify mutants that undergo transient cell fusion involving cytosol exchange but not karyogamy, and show this drives distinct cell fates in the two gametes: The P-partner undergoes lethal, haploid meiosis while the M-cell persists in mating. Consistently, we find that the zygotic transcription that drives meiosis is initiated rapidly only from the P-parental genome, even in wild type cells. This asymmetric gene expression depends on a bi-partite complex formed post-fusion between the nuclear P-cell-specific homeobox protein Pi and a cytosolic M-specific peptide Mi7,8, which is captured by Pi in the P-nucleus. Zygotic transcription is thus poised to initiate in the P-nucleus as fast as Mi reaches it. The asymmetric nuclear accumulation is inherent to the transcription factor design, and is reconstituted by a pair of synthetic interactors, one localized to the nucleus of one gamete and the other in the cytosol of its partner. Strikingly, imposing a delay in zygotic transcription, by postponing Mi expression or deleting its transcriptional target in the P-genome, leads to zygotes fusing with additional gametes, thus forming polyploids and eventually aneuploid progeny. We further show that the signaling cascade to block re-fertilization shares components with, but bifurcates from, meiotic induction9-11. Thus, cytoplasmic connection upon gamete fusion leads to rapid reconstitution of a bi-partite transcription factor in one partner to block re-fertilization and induce meiosis, thus ensuring genome maintenance during sexual reproduction.