Rtt106p is a histone chaperone involved in heterochromatin-mediated silencing

Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13410-5. doi: 10.1073/pnas.0506176102. Epub 2005 Sep 12.

Abstract

Epigenetic inheritance of heterochromatin structure is an important cellular process whose mechanism remains elusive. In this article, we describe the identification of nine enhancers of the silencing defect of a Saccharomyces cerevisiae-PCNA mutant by screening a library of approximately 4,700 viable yeast deletion mutants. Of the nine mutants identified, six (hir1, hir3, sas2, sas4, sas5, and sir1) were previously known to reduce silencing synergistically with a mutation in Cac1p, the large subunit of chromatin assembly factor 1 (CAF-1). The predicted gene products that are affected in three other mutants (nam7, msh2, and rtt106) have not been implicated previously in silencing. Characterization of the rtt106Delta allele revealed that it synergistically reduced heterochromatin silencing when combined with a mutation in Cac1p but not with a mutation in Asf1p (a histone H3 and H4 chaperone). Moreover, Rtt106p interacted with histones H3 and H4 both in vitro and in vivo, and it displayed a nucleosome assembly activity in vitro. Furthermore, Rtt106p interacts with CAF-1 physically through Cac1p. These biochemical and genetic data indicate that Rtt106p is a previously uncharacterized histone chaperone connecting S phase to epigenetic inheritance.

Publication types

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

MeSH terms

  • Chromatin Assembly and Disassembly / physiology*
  • Epigenesis, Genetic / physiology
  • Gene Deletion
  • Gene Expression Regulation, Fungal / physiology*
  • Gene Silencing / physiology*
  • Histones / genetics
  • Histones / metabolism*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Ribonucleases / genetics
  • Ribonucleases / metabolism
  • S Phase / physiology
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Histones
  • Molecular Chaperones
  • Proliferating Cell Nuclear Antigen
  • Rtt106 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Ribonucleases
  • POP2 protein, S cerevisiae