Constraining G1-specific transcription to late G1 phase: the MBF-associated corepressor Nrm1 acts via negative feedback

Mol Cell. 2006 Aug;23(4):483-96. doi: 10.1016/j.molcel.2006.06.025.

Abstract

G1-specific transcription in yeast depends upon SBF and MBF. We have identified Nrm1 (negative regulator of MBF targets 1), as a stable component of MBF. NRM1 (YNR009w), an MBF-regulated gene expressed during late G1 phase, associates with G1-specific promoters via MBF. Transcriptional repression upon exit from G1 phase requires both Nrm1 and MBF. Inactivation of Nrm1 results in prolonged expression of MBF-regulated transcripts and leads to hydroxyurea (HU) resistance and enhanced bypass of rad53Delta- and mec1Delta-associated lethality. Constitutive expression of a stabilized form of Nrm1 represses MBF targets and leads to HU sensitivity. The fission yeast homolog SpNrm1, encoded by the MBF target gene nrm1(+) (SPBC16A3.07c), binds to MBF target genes and acts as a corepressor. In both yeasts, MBF represses G1-specific transcription outside of G1 phase. A negative feedback loop involving Nrm1 bound to MBF leads to transcriptional repression as cells exit G1 phase.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Cell Cycle Proteins / metabolism
  • Checkpoint Kinase 2
  • Feedback, Physiological*
  • G1 Phase*
  • Gene Expression Regulation, Fungal
  • Genes, Fungal / genetics
  • Hydroxyurea / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation / genetics
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Schizosaccharomyces / metabolism
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism
  • Transcription, Genetic* / drug effects

Substances

  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • MBF1 protein, S cerevisiae
  • Nrm1 protein, S cerevisiae
  • RNA, Messenger
  • Repressor Proteins
  • SBF protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factors
  • Checkpoint Kinase 2
  • MEC1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • RAD53 protein, S cerevisiae
  • Hydroxyurea