Heterochromatin renewal after release from growth arrest controls genome-wide transcription re-activation in S.cerevisiae

The budding yeast SIR complex (Silent Information Regulator) is the principal actor in heterochromatin formation, which causes epigenetically regulated gene silencing phenotypes. The dynamics of the SIR complex during the cell cycle are however not well understood. It is consequently still not known how the SIR complex is maintained and/or restored after genome replication and cell division, and how the underlying silenced state is transmitted form one cell generation to the next. We used the tag switch RITE system to measure genome wide turnover rates of the SIR subunit Sir3p during and after exit from growth arrest caused by nutrient depletion. Our results show that Sir3p subunits have high rates of exchange immediately after release from growth arrest. Maternal Sir3p is consequently almost completely replaced with newly synthesized Sir3p in subtelomeric regions by the end of the first cell cycle after release from growth arrest. The sudden increase in the off rate of Sir3 upon release from growth arrest leads to SIR complex instability that is exacerbated in strains with sub optimal amounts of newly synthesized Sir3p. Unexpectedly, heightened SIR complex instability in these Sir3p hypo-morphs has global effects on gene expression with faster reactivation of hundreds of euchromatic genes upon exit from growth arrest.