Mutations in the nucleosome core enhance transcriptional silencing

Eugenia Y. Xu, Xin Bi, Michael J. Holland, Daniel E. Gottschling, James R. Broach

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Transcriptional silencing in Saccharomyces requires specific nucleosome modifications promoted in part by a complex of Sir proteins that binds to the modified nucleosomes. Recent evidence suggests that modifications of both the histone amino termini and the core domain of nucleosomes contribute to silencing. We previously identified histone H4 mutations affecting residues in the core of the nucleosome that yield enhanced silencing at telomeres. Here we show that enhanced silencing induced by these mutations increases the proportion of cells in which telomeres and silent mating-type loci are in the silent state. One H4 mutation affects the expression of a subset of genes whose expression is altered by deletion of HTZ1, which encodes the histone variant H2A.Z, suggesting that the mutation may antagonize H2A.Z incorporation into nucleosomes. A second mutation causes the spread of silencing into subtelomeric regions that are not normally silenced in wild-type cells. Mechanistically, this mutation does not significantly accelerate the formation of silent chromatin but, rather, reduces the rate of decay of the silenced state. We propose that these mutations use distinct mechanisms to affect the dynamic interplay between activation and repression at the boundary between active and silent chromatin.

Original languageEnglish (US)
Pages (from-to)1846-1859
Number of pages14
JournalMolecular and cellular biology
Volume25
Issue number5
DOIs
StatePublished - Mar 2005

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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