Activation of the G₂/M-Specific Gene CLB2 Requires Multiple Cell Cycle Signals

Abstract

In budding yeast (Saccharomyces cerevisiae), the periodic expression of the G₂/M-specific gene CLB2 depends on a DNA binding complex that mediates its repression during G₁ and activation from the S phase to the exit of mitosis. The switch from low to high expression levels depends on the transcriptional activator Ndd1. We show that the inactivation of the Sin3 histone deacetylase complex bypasses the essential role of Ndd1 in cell cycle progression. Sin3 and its catalytic subunit Rpd3 associate with the CLB2 promoter during the G₁ phase of the cell cycle. Both proteins dissociate from the promoter at the onset of the S phase and reassociate during G₂ phase. Sin3 removal coincides with a transient increase in histone H4 acetylation followed by the expulsion of at least one nucleosome from the promoter region. Whereas the first step depends on Cdc28/Cln1 activity, Ndd1 function is required for the second step. Since the removal of Sin3 is independent of Ndd1 recruitment and Cdc28/Clb activity it represents a unique regulatory step which is distinct from transcriptional activation.

We thank Veerle De Wever for fruitful discussion and critical reading of the manuscript and Christoph Langer for technical assistance in one experiment.