Recruitment of Cln3 cyclin to promoters controls cell cycle entry via histone deacetylase and other targets.
In yeast, the G1 cyclin Cln3 promotes cell cycle entry by activating the transcription factor SBF. In mammals, there is a parallel system for cell cycle entry in which cyclin dependent kinase (CDK) activates transcription factor E2F/Dp. Here we show that Cln3 regulates SBF by at least two different pathways, one involving the repressive protein Whi5, and the second involving Stb1. The Rpd3 histone deacetylase complex is also involved. Cln3 binds to SBF at the CLN2 promoter, and removes previously bound Whi5 and histone deacetylase. Adding extra copies of the SBF binding site to the cell delays Start, possibly by titrating Cln3. Since Rpd3 is the yeast ortholog of mammalian HDAC1, there is now a virtually complete analogy between the proteins regulating cell cycle entry in yeast (SBF, Cln3, Whi5 and Stb1, Rpd3) and mammals (E2F, Cyclin D, Rb, HDAC1). The cell may titrate Cln3 molecules against the number of SBF binding sites, and this could be the underlying basis of the size-control mechanism for Start.
Wang
Hongyin
H
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA.
Carey
Lucas B
LB
Cai
Ying
Y
Wijnen
Herman
H
Futcher
Bruce
B
D016213:Cyclins / Q000378:metabolism*; D016193:G1 Phase / Q000187:drug effects*; D006655:Histone Deacetylases / Q000378:metabolism*; D012097:Repressor Proteins / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
C079895:CLN3 protein, S cerevisiae; D016213:Cyclins; D012097:Repressor Proteins; C081540:SBF protein, S cerevisiae; C120525:STB1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C508130:Whi5 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases