Chromatin disassembly mediated by the histone chaperone Asf1 is essential for transcriptional activation of the yeast PHO5 and PHO8 genes

Mol Cell. 2004 Jun 4;14(5):657-66. doi: 10.1016/j.molcel.2004.05.016.

Abstract

Nucleosome loss from a promoter region has recently been described as a potential mechanism for transcriptional regulation. We investigated whether H3/H4 histone chaperones mediate the loss of nucleosomes from the promoter of the yeast PHO5 gene during transcriptional activation. We found that antisilencing function 1 (Asf1p) mediates nucleosome disassembly from the PHO5 promoter in vivo. We show that nucleosome disassembly also occurs at a second promoter, that of the PHO8 gene, during activation, and we demonstrate that this is also mediated by Asf1p. Furthermore, we show that nucleosome disassembly is essential for PHO5 and PHO8 activation. Contrary to the current dogma, we demonstrate that nucleosome disassembly is not required to enable binding of the Pho4p activator to its PHO5 UASp2 site in vivo. Finally, we show that nucleosomes are reassembled over the PHO5 promoter during repression. As such, nucleosome disassembly and reassembly are important mechanisms for transcriptional activation and repression, respectively.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acid Phosphatase
  • Binding Sites / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromatin Assembly and Disassembly / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Fungal / genetics*
  • Histones / genetics
  • Histones / metabolism
  • Models, Molecular
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Promoter Regions, Genetic / genetics*
  • Protein Binding / physiology
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation / genetics*
  • Yeasts / genetics
  • Yeasts / metabolism*

Substances

  • ASF1 protein, S cerevisiae
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Histones
  • Molecular Chaperones
  • Nucleosomes
  • PHO4 protein, S cerevisiae
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • thiamine-binding protein
  • Acid Phosphatase
  • PHO3 protein, S cerevisiae
  • PHO5 protein, S cerevisiae