Recruitment of Cln3 Cyclin to Promoters Controls Cell Cycle Entry via Histone Deacetylase and Other Targets

Abstract

In yeast, titration of an increasing number of molecules of the G1 cyclin Cln3 by a fixed number of DNA-bound molecules of the transcription factor SBF might underlie the dependence of cell cycle entry on cell size.

The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation

“…Perhaps, indirectly, Ydj1 could also be required for proper sBF and mBF function (dashed arrow). Cln1 and Cln2 cyclins generate a positive feedback loop essential for coherent and robust sBF and mBF activation [25][26][27] , and stb1 is a transcriptional modulator that contributes to inhibit sBF-and mBF-dependent transcription during G1 48 . sfp1 acts as a negative regulator of start (continuous arrow) and, as it is a transcription activator in ribosome biogenesis, sfp1 would also upregulate Cln3 levels (dashed arrow) as a result of increased translation 4 .…”

“…Cells simultaneously lacking activating (Cln3) and inhibiting (Whi5, Stb1) components of the Start network display a budding size very similar to wild-type cells 48 . Accordingly, when we analysed cln3 whi5N stb1 cells by time-lapse microscopy, we found that average cell volume at Start was very similar to wild-type cells (Supplementary Table S6).…”

Free Histones and the Cell Cycle

“…Interestingly, depletion of human Spt16 leads to the repression of H1, H2A and H2B genes (Li et al, 2007), which could be the result of the accumulation of the free histones in human cells after FACT dysfunction. Given the analogy between the G1-S regulators in yeast (Cln3-SBF-Whi5-Rpd3) and mammals (CyclinD1-E2F-Rb-HDAC1) (Wang et al, 2009;Takahata et al, 2009), the functional link between the accumulation of free histones and the regulation of the G1-S transition may be evolutionarily conserved. This chapter emphasises that excess free histones may have serious implications for the normal progression of DNA replication when the toxicity of free histones is maximal in the S-phase (Gunjan & Verreault, 2003).…”

Cell Cycle Regulation of DNA Replication in S. cerevisiae

“…Whi5 is a transcriptional suppressor that interacts with SBF, a transcription factor complex required for transcription of genes involved in cell cycle entry and DNA replication (the socalled G1 transcriptional program). Whi5 also recruits histone deacetylases (HDACs) that maintain the chromatin surrounding the SBF-Whi5 complex in a repressive state (Huang, Kaluarachchi et al 2009;Wang, Carey et al 2009). Thus, as long as Whi5 is bound to SBF, the cell cannot enter the cell cycle.…”

“…Thus, as long as Whi5 is bound to SBF, the cell cannot enter the cell cycle. However, phosphorylation of Whi5 by Cln3-Cdk1 induces the release of Whi5 and HDACs from SBF (Costanzo, Nishikawa et al 2004;de Bruin, McDonald et al 2004;Huang, Kaluarachchi et al 2009;Wang, Carey et al 2009). SBF then activates transcription of the G1 transcriptional program.…”