APC/C-dependent control of gene expression and cell identity

Metazoan development requires robust proliferation of progenitor cells, whose identities are established by tightly controlled transcriptional networks (1). As gene expression is globally inhibited during mitosis, the transcriptional programs defining cell identity must be restarted in each cell cycle (2-5), yet how this is accomplished is poorly understood. Here, we identified a ubiquitin-dependent mechanism that integrates gene expression with cell division to preserve cell identity. We found that WDR5 and TBP, which bind active interphase promoters (6,7), recruit the anaphase-promoting complex (APC/C) to specific transcription start sites (TSS) during mitosis. This allows APC/C to decorate histones with K11/K48-branched ubiquitin chains that recruit p97/VCP and the proteasome and ensure rapid expression of pluripotency genes in the next cell cycle. Mitotic exit and transcription re-initiation are thus controlled by the same regulator, APC/C, which provides a robust mechanism to maintain cell identity through cell division.