Repression of G1/S transcription is mediated via interaction of the GTB motifs of Nrm1 and Whi5 with Swi6

Mol Cell Biol. 2013 Apr;33(8):1476-86. doi: 10.1128/MCB.01333-12. Epub 2013 Feb 4.

Abstract

In Saccharomyces cerevisiae, G1/S transcription factors MBF and SBF regulate a large family of genes important for entry to the cell cycle and DNA replication and repair. Their regulation is crucial for cell viability, and it is conserved throughout evolution. MBF and SBF consist of a common component, Swi6, and a DNA-specific binding protein, Mbp1 and Swi4, respectively. Transcriptional repressors bind to and regulate the activity of both transcription factors. Whi5 binds to SBF and represses its activity at the beginning of the G1 phase to prevent early activation. Nrm1 binds to MBF to repress transcription as cells progress through S phase. Here, we describe a protein motif, the GTB motif (for G1/S transcription factor binding), in Nrm1 and Whi5 that is required to bind to the transcription factors. We also identify a region of the carboxy terminus of Swi6 that is required for Nrm1 and Whi5 binding to their target transcription factors and show that mutation of this region overrides the repression of MBF- and SBF-regulated genes by Nrm1 and Whi5. Finally, we show that the GTB motif is the core of a functional module that is necessary and sufficient for targeting of the transcription factors by their cognate repressors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • DNA-Binding Proteins / metabolism
  • G1 Phase
  • Gene Expression Regulation, Fungal
  • Hydroxyurea / pharmacology
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Tertiary
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • S Phase
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Sequence Alignment
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transcription, Genetic*

Substances

  • DNA-Binding Proteins
  • MBP1 protein, S cerevisiae
  • Nrm1 protein, S cerevisiae
  • Repressor Proteins
  • SBF protein, S cerevisiae
  • SWI6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Whi5 protein, S cerevisiae
  • Hydroxyurea