Journal article
Simultaneous Mutation of Methylated Lysine Residues in Histone H3 Causes Enhanced Gene Silencing, Cell Cycle Defects, and Cell Lethality in Saccharomyces cerevisiae
Molecular and cellular biology, Vol.27(19), pp.6832-6841
10/2007
Handle:
https://hdl.handle.net/2376/114160
PMCID: PMC2099221
PMID: 17664279
Abstract
The methylation of specific lysine residues in histone H3 is integral to transcription regulation; however, little is known about how combinations of methylated lysine residues act in concert to regulate genome-wide transcription. We have systematically mutated methylated histone lysine residues in yeast and found that the triple mutation of H3K4, H3K36, and H3K79 to arginine (H3 K4,36,79R) is lethal. The histone H3 K4,36,79R mutant causes a mitotic cell cycle delay and a progressive transcription defect that initiates in telomere regions and then spreads into the chromosome. This effect is mediated by the silent information regulator (SIR) silencing complex, as we observe increased binding of the SIR complex to genomic regions adjacent to yeast telomeres in the H3 K4,36,79R mutant and deletion of
SIR2
,
SIR3
, or
SIR4
rescues the lethal phenotype. Curiously, a yeast strain in which the histone methyltransferase genes are simultaneously deleted is viable. Indeed, deletion of the histone methyltransferase genes can suppress the H3 K4,36,79R lethal phenotype. These and other data suggest that the cause of lethality may in part be due to the association of histone methyltransferase enzymes with a histone substrate that cannot be methylated.
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Details
- Title
- Simultaneous Mutation of Methylated Lysine Residues in Histone H3 Causes Enhanced Gene Silencing, Cell Cycle Defects, and Cell Lethality in Saccharomyces cerevisiae
- Creators
- Yi Jin - Molecular Plant SciencesAmy M Rodriguez - Molecular Plant SciencesJulie D Stanton - Molecular Plant SciencesAna A Kitazono - Molecular Plant SciencesJohn J Wyrick - Molecular Plant Sciences
- Publication Details
- Molecular and cellular biology, Vol.27(19), pp.6832-6841
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- American Society for Microbiology (ASM)
- Identifiers
- 99900548484901842
- Language
- English
- Resource Type
- Journal article