Fission yeast Whi5 represses MBF-dependent transcription in quiescent cells

When cells arrest in G1 to enter quiescence, the transcriptional machinery that drives the G1/S transition must be inactivated. In budding yeast and mammals, this repression is mediated by the Whi5 and Retinoblastoma (Rb) proteins, which inhibit the SBF and E2F transcription factors, respectively. In fission yeast, the MBF complex is functionally analogous to SBF and E2F, and Whi5/Mug54 has been predicted to act as a G1/S transcriptional repressor. Here, we show that upon nitrogen starvation, Whi5 accumulates in the nucleus and is required to repress MBF-dependent genes during quiescence. Mass spectrometry and bimolecular fluorescence complementation (BiFC) demonstrate that Whi5 physically associates with components of both the MBF complex and the histone deacetylase Clr6-I complex. Moreover, Whi5 is required for the interaction between MBF and Clr6-I, supporting a model in which Whi5 represses MBF-dependent genes in quiescent cells by recruiting HDAC activity to their promoters.