Linking Cell Cycle to Histone Modifications: SBF and H2B Monoubiquitination Machinery and Cell-Cycle Regulation of H3K79 Dimethylation

Julia M. Schulze; Jessica Jackson; Shima Nakanishi; Jennifer M. Gardner; Thomas Hentrich; Jeff Haug; Mark Johnston; Sue L. Jaspersen; Michael S. Kobor; Ali Shilatifard

doi:10.1016/j.molcel.2009.07.017

Linking Cell Cycle to Histone Modifications: SBF and H2B Monoubiquitination Machinery and Cell-Cycle Regulation of H3K79 Dimethylation

Julia M. Schulze, Jessica Jackson, Shima Nakanishi, Jennifer M. Gardner, Thomas Hentrich, Jeff Haug, Mark Johnston, Sue L. Jaspersen, Michael S. Kobor, Ali Shilatifard^*

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

146 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	626-641
Number of pages	16
Journal	Molecular cell
Volume	35
Issue number	5
DOIs	https://doi.org/10.1016/j.molcel.2009.07.017
State	Published - Sep 11 2009

Funding

We thank Edwin Smith for critical reading of this manuscript and Laura Shilatifard for editorial assistance. Furthermore, we thank Raphael Gottardo for providing the MAT package to analyze the ChIP-on-chip data, Hunter Fraser for help with the statistical analysis, and Frank Holstege and Harm van Bakel for detailed ChIP-on-chip protocols using double-round T7 amplification. J.M.S. is supported by a fellowship from the German Academic Exchange Service and a graduate studentship from the Child and Family Research Institute. M.S.K. is a Scholar of the Michael Smith Foundation for Health Research and the Canadian Institute for Advanced Research. Research for this study in the laboratory of M.S.K. was supported by an operating grant from the Canadian Institute of Health Research (MOP-79442). S.N. is a Fellow of the Leukemia and Lymphoma Society. The work in Shilatifard's laboratory was supported by a grant from the National Institute of Health (GM069905) to A.S.H.

Keywords

CELLCYCLE
DNA
PROTEINS

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2009.07.017

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@article{453a3fa597b341f28a38e7adb9b02a0f,

title = "Linking Cell Cycle to Histone Modifications: SBF and H2B Monoubiquitination Machinery and Cell-Cycle Regulation of H3K79 Dimethylation",

abstract = "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.",

keywords = "CELLCYCLE, DNA, PROTEINS",

author = "Schulze, {Julia M.} and Jessica Jackson and Shima Nakanishi and Gardner, {Jennifer M.} and Thomas Hentrich and Jeff Haug and Mark Johnston and Jaspersen, {Sue L.} and Kobor, {Michael S.} and Ali Shilatifard",

note = "Funding Information: We thank Edwin Smith for critical reading of this manuscript and Laura Shilatifard for editorial assistance. Furthermore, we thank Raphael Gottardo for providing the MAT package to analyze the ChIP-on-chip data, Hunter Fraser for help with the statistical analysis, and Frank Holstege and Harm van Bakel for detailed ChIP-on-chip protocols using double-round T7 amplification. J.M.S. is supported by a fellowship from the German Academic Exchange Service and a graduate studentship from the Child and Family Research Institute. M.S.K. is a Scholar of the Michael Smith Foundation for Health Research and the Canadian Institute for Advanced Research. Research for this study in the laboratory of M.S.K. was supported by an operating grant from the Canadian Institute of Health Research (MOP-79442). S.N. is a Fellow of the Leukemia and Lymphoma Society. The work in Shilatifard's laboratory was supported by a grant from the National Institute of Health (GM069905) to A.S.H. ",

year = "2009",

month = sep,

day = "11",

doi = "10.1016/j.molcel.2009.07.017",

language = "English (US)",

volume = "35",

pages = "626--641",

journal = "Molecular cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "5",

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T1 - Linking Cell Cycle to Histone Modifications

T2 - SBF and H2B Monoubiquitination Machinery and Cell-Cycle Regulation of H3K79 Dimethylation

AU - Schulze, Julia M.

AU - Jackson, Jessica

AU - Nakanishi, Shima

AU - Gardner, Jennifer M.

AU - Hentrich, Thomas

AU - Haug, Jeff

AU - Johnston, Mark

AU - Jaspersen, Sue L.

AU - Kobor, Michael S.

AU - Shilatifard, Ali

N1 - Funding Information: We thank Edwin Smith for critical reading of this manuscript and Laura Shilatifard for editorial assistance. Furthermore, we thank Raphael Gottardo for providing the MAT package to analyze the ChIP-on-chip data, Hunter Fraser for help with the statistical analysis, and Frank Holstege and Harm van Bakel for detailed ChIP-on-chip protocols using double-round T7 amplification. J.M.S. is supported by a fellowship from the German Academic Exchange Service and a graduate studentship from the Child and Family Research Institute. M.S.K. is a Scholar of the Michael Smith Foundation for Health Research and the Canadian Institute for Advanced Research. Research for this study in the laboratory of M.S.K. was supported by an operating grant from the Canadian Institute of Health Research (MOP-79442). S.N. is a Fellow of the Leukemia and Lymphoma Society. The work in Shilatifard's laboratory was supported by a grant from the National Institute of Health (GM069905) to A.S.H.

PY - 2009/9/11

Y1 - 2009/9/11

N2 - 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.

AB - 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.

KW - CELLCYCLE

KW - DNA

KW - PROTEINS

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U2 - 10.1016/j.molcel.2009.07.017

DO - 10.1016/j.molcel.2009.07.017

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AN - SCOPUS:69749117490

SN - 1097-2765

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JO - Molecular cell

JF - Molecular cell

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ER -

Linking Cell Cycle to Histone Modifications: SBF and H2B Monoubiquitination Machinery and Cell-Cycle Regulation of H3K79 Dimethylation

Abstract

Funding

Keywords

ASJC Scopus subject areas

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