HP1 proteins form distinct complexes and mediate heterochromatic gene silencing by nonoverlapping mechanisms

Mol Cell. 2008 Dec 26;32(6):778-90. doi: 10.1016/j.molcel.2008.10.026.

Abstract

HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing. In fission yeast, two HP1 homologs, Swi6 and Chp2, function in heterochromatic gene silencing, but their relative contribution to silencing remains unknown. Here we show that Swi6 and Chp2 exist in nonoverlapping complexes and make distinct contributions to silencing. Chp2 associates with the SHREC histone deacetylase complex (SHREC2), is required for histone H3 lysine 14 (H3K14) deacetylation, and mediates transcriptional repression by limiting RNA polymerase II access to heterochromatin. In contrast, Swi6 associates with a different set of nuclear proteins and with noncoding centromeric transcripts and is required for efficient RNAi-dependent processing of these transcripts. Our findings reveal an unexpected role for Swi6 in RNAi-mediated gene silencing and suggest that different HP1 proteins ensure full heterochromatic gene silencing through largely nonoverlapping inhibitory mechanisms.

Publication types

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

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Centromere / metabolism
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Gene Expression Regulation, Fungal
  • Gene Silencing*
  • Heterochromatin / metabolism*
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Lysine / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Multiprotein Complexes / metabolism*
  • Nuclear Proteins / metabolism
  • Protein Binding
  • RNA Polymerase II / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / chemistry
  • Repressor Proteins / isolation & purification
  • Repressor Proteins / metabolism*
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / isolation & purification
  • Schizosaccharomyces pombe Proteins / metabolism*

Substances

  • CHP2 protein, S pombe
  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • Histones
  • Multiprotein Complexes
  • Nuclear Proteins
  • RNA, Messenger
  • Repressor Proteins
  • Schizosaccharomyces pombe Proteins
  • Swi6 protein, S pombe
  • Chromobox Protein Homolog 5
  • RNA Polymerase II
  • Histone Deacetylases
  • Lysine