Yng2p-dependent NuA4 histone H4 acetylation activity is required for mitotic and meiotic progression.
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.
Choy
J S
JS
Center for Molecular Oncology, Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois 60637, USA.
Tobe
B T
BT
Huh
J H
JH
Kron
S J
SJ
D000107:Acetylation; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D008540:Meiosis / Q000502:physiology*; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D015739:Nocodazole / Q000494:pharmacology; D010940:Plant Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins
D006657:Histones; D018398:Homeodomain Proteins; D010940:Plant Proteins; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; C438844:Yng2p protein, plant; D015739:Nocodazole