Linking cell cycle to histone modifications: SBF and H2B monoubiquitination machinery and cell-cycle regulation of H3K79 dimethylation.
To identify regulators involved in determining the differential pattern of H3K79 methylation by Dot1, we screened the entire yeast gene deletion collection by GPS for genes required for normal levels of H3K79 di- but not trimethylation. We identified the cell cycle-regulated SBF protein complex required for H3K79 dimethylation. We also found that H3K79 di- and trimethylation are mutually exclusive, with M/G1 cell cycle-regulated genes significantly enriched for H3K79 dimethylation. Since H3K79 trimethylation requires prior monoubiquitination of H2B, we performed genome-wide profiling of H2BK123 monoubiquitination and showed that H2BK123 monoubiquitination is not detected on cell cycle-regulated genes and sites containing H3K79me2, but is found on H3K79me3-containing regions. A screen for genes responsible for the establishment/removal of H3K79 dimethylation resulted in identification of NRM1 and WHI3, both of which impact the transcription by the SBF and MBF protein complexes, further linking the regulation of methylation status of H3K79 to the cell cycle.
Schulze
Julia M
JM
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, BC, Canada.
Jackson
Jessica
J
Nakanishi
Shima
S
Gardner
Jennifer M
JM
Hentrich
Thomas
T
Haug
Jeff
J
Johnston
Mark
M
Jaspersen
Sue L
SL
Kobor
Michael S
MS
Shilatifard
Ali
A
D002453:Cell Cycle / Q000235:genetics; D021901:DNA, Intergenic; D004268:DNA-Binding Proteins / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015966:Gene Expression Regulation, Fungal; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008239:Lysine; D008745:Methylation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
C472168:Bre1 protein, S cerevisiae; D021901:DNA, Intergenic; D004268:DNA-Binding Proteins; D006657:Histones; C513403:Nrm1 protein, S cerevisiae; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C081540:SBF protein, S cerevisiae; C062214:SWI4 protein, S cerevisiae; C075111:SWI6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C440012:Whi3 protein, S cerevisiae; C416235:Dot1 protein, S cerevisiae; D011495:Histone-Lysine N-Methyltransferase; C471606:RAD6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D008239:Lysine
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