Yng2p-dependent NuA4 histone H4 acetylation activity is required for mitotic and meiotic progression

J Biol Chem. 2001 Nov 23;276(47):43653-62. doi: 10.1074/jbc.M102531200. Epub 2001 Sep 5.

Abstract

In all eukaryotes, multisubunit histone acetyltransferase (HAT) complexes acetylate the highly conserved lysine residues in the amino-terminal tails of core histones to regulate chromatin structure and gene expression. One such complex in yeast, NuA4, specifically acetylates nucleosome-associated histone H4. Recent studies have revealed that NuA4 comprises at least 11 subunits, including Yng2p, a yeast homolog of the candidate human tumor suppressor gene, ING1. Consistent with prior data, we find that cells lacking Yng2p are deficient for NuA4 activity and are temperature-sensitive. Furthermore, we show that the NuA4 complex is present in the absence of Yng2p, suggesting that Yng2p functions to maintain or activate NuA4 HAT activity. Sporulation of diploid yng2 mutant cells reveals a defect in meiotic progression, whereas synchronized yng2 mutant cells display a mitotic delay. Surprisingly, genome-wide expression analysis revealed little change from wild type. Nocodazole arrest and release relieves the mitotic defects, suggesting that Yng2p may have a critical function prior to or during metaphase. Rather than a uniform decrease in acetylated forms of histone H4, we find striking cell-to-cell heterogeneity in the loss of acetylated histone H4 in yng2 mutant cells. Treating yng2 mutants with the histone deacetylase inhibitor trichostatin A suppressed the mitotic delay and restored global histone H4 acetylation, arguing that reduced H4 acetylation may underlie the cell cycle delay.

Publication types

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

MeSH terms

  • Acetylation
  • Histones / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Meiosis / physiology*
  • Mitosis / drug effects
  • Mitosis / physiology*
  • Nocodazole / pharmacology
  • Plant Proteins*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Transcription, Genetic
  • Tumor Suppressor Proteins*

Substances

  • Histones
  • Homeodomain Proteins
  • Plant Proteins
  • Saccharomyces cerevisiae Proteins
  • Tumor Suppressor Proteins
  • Yng2p protein, plant
  • Nocodazole