Molecular Genetics and Genomics

, Volume 277, Issue 5, pp 491–506

The role of histone ubiquitylation and deubiquitylation in gene expression as determined by the analysis of an HTB1K123RSaccharomyces cerevisiae strain

  • A. Irina Mutiu
  • Stephen M. T. Hoke
  • Julie Genereaux
  • Gaoyang Liang
  • Christopher J. Brandl
Original Paper

DOI: 10.1007/s00438-007-0212-6

Cite this article as:
Mutiu, A.I., Hoke, S.M.T., Genereaux, J. et al. Mol Genet Genomics (2007) 277: 491. doi:10.1007/s00438-007-0212-6

Abstract

In Saccharomyces cerevisiae histone H2B is ubiquitylated at lysine 123 in a process requiring the E2-ubiquitin conjugase, Rad6. We have analyzed gene expression in a strain containing a variant of histone H2B with lysine 123 converted to arginine to address the mechanisms by which ubiquitylation and deubiquitylation of histone H2B affect gene expression. The SAGA complex component, Ubp8, is one of two proteases that remove the ubiquitin moiety at lysine 123. We show that changes in gene expression observed upon deletion of ubp8 are suppressed by htb1K123R, which provides genetic evidence that Ubp8 alters gene expression through deubiquitylation of histone H2B. Microarray analyses of the htb1K123R strain show that loss of histone ubiquitylation results in a twofold or greater change in expression of ∼1.5% of the protein coding genes with ∼75% of these increasing. For genes in which ubiquitylation represses expression, ubiquitylation principally acts through its effects on histone methylation. In contrast, decreased expression of the CWP1 gene was not paralleled by deletions of methyltransferase components and is thus likely independent of methylation. Finally, by comparing gene expression changes in the htb1K123R strain with those in a strain deleted for rad6, we conclude that lysine 123 affects transcription primarily because of it being a site of ubiquitylation.

Keywords

TranscriptionYeastUbp8Histone deubiquitylationSAGA complex

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • A. Irina Mutiu
    • 1
  • Stephen M. T. Hoke
    • 1
  • Julie Genereaux
    • 1
  • Gaoyang Liang
    • 1
    • 2
  • Christopher J. Brandl
    • 1
  1. 1.Department of Biochemistry, Schulich School of Medicine and DentistryUniversity of Western OntarioLondonCanada
  2. 2.Department of Biochemistry and BiophysicsUniversity of North Carolina at Chapel HillChapel HillUSA