Forkhead proteins control the outcome of transcription factor binding by antiactivation

EMBO J. 2007 Oct 17;26(20):4324-34. doi: 10.1038/sj.emboj.7601859. Epub 2007 Sep 27.

Abstract

Transcription factors with identical DNA-binding specificity often activate different genes in vivo. Yeast Ace2 and Swi5 are such activators, with targets we classify as Swi5-only, Ace2-only, or both. We define two unique regulatory modes. Ace2 and Swi5 both bind in vitro to Swi5-only genes such as HO, but only Swi5 binds and activates in vivo. In contrast, Ace2 and Swi5 both bind in vivo to Ace2-only genes, such as CTS1, but promoter-bound Swi5 fails to activate. We show that activation by Swi5 is prevented by the binding of the Forkhead factors Fkh1 and Fkh2, which recruit the Rpd3(Large) histone deacetylase complex to the CTS1 promoter. Global analysis shows that all Ace2-only genes are bound by both Ace2 and Swi5, and also by Fkh1/2. Genes normally activated by either Ace2 or Swi5 can be converted to Ace2-only genes by the insertion of Fkh-binding sites. Thus Fkh proteins, which function initially to activate SWI5 and ACE2, subsequently function as Swi5-specific antiactivators.

Publication types

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

MeSH terms

  • Acetylation
  • Cell Cycle
  • Chromatin Immunoprecipitation
  • DNA / chemistry
  • DNA-Binding Proteins / chemistry*
  • Forkhead Transcription Factors / metabolism*
  • Fungal Proteins / chemistry*
  • Gene Expression Regulation, Fungal
  • Histones / chemistry
  • Open Reading Frames
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*

Substances

  • ACE2 protein, S cerevisiae
  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Fungal Proteins
  • Histones
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • DNA