β-N-acetylglucosamine (O-GlcNAc) is part of the histone code

Kaoru Sakabe, Zihao Wang, Gerald Warren Hart

Research output: Contribution to journalArticle

Abstract

Dynamic posttranslational modification of serine and threonine residues of nucleocytoplasmic proteins by β-N-acetylglucosamine (O-GlcNAc) is a regulator of cellular processes such as transcription, signaling, and protein-protein interactions. Like phosphorylation, O-GlcNAc cycles in response to a wide variety of stimuli. Although cycling of O-GlcNAc is catalyzed by only two highly conserved enzymes, O-GlcNAc transferase (OGT), which adds the sugar, and β-N-acetylglucosaminidase (O-GlcNAcase), which hydrolyzes it, the targeting of these enzymes is highly specific and is controlled by myriad interacting subunits. Here, we demonstrate by multiple specific immunological and enzymatic approaches that histones, the proteins that package DNA within the nucleus, are O-GlcNAcylated in vivo. Histones also are substrates for OGT in vitro. We identify O-GlcNAc sites on histones H2A, H2B, and H4 using mass spectrometry. Finally, we show that histone O-GlcNAcylation changes during mitosis and with heat shock. Taken together, these data show that O-GlcNAc cycles dynamically on histones and can be considered part of the histone code.

Original languageEnglish (US)
Pages (from-to)19915-19920
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number46
DOIs
StatePublished - Nov 16 2010

Fingerprint

Histone Code
Acetylglucosamine
Histones
Proteins
Acetylglucosaminidase
Enzymes
Threonine
Post Translational Protein Processing
Mitosis
Serine
Shock
Mass Spectrometry
Hot Temperature
Phosphorylation
DNA

Keywords

  • Epigenetics
  • Histones

ASJC Scopus subject areas

  • General

Cite this

β-N-acetylglucosamine (O-GlcNAc) is part of the histone code. / Sakabe, Kaoru; Wang, Zihao; Hart, Gerald Warren.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 46, 16.11.2010, p. 19915-19920.

Research output: Contribution to journalArticle

Sakabe, Kaoru ; Wang, Zihao ; Hart, Gerald Warren. / β-N-acetylglucosamine (O-GlcNAc) is part of the histone code. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 46. pp. 19915-19920.
@article{182259940518483eaf3641b6f2869aac,
title = "β-N-acetylglucosamine (O-GlcNAc) is part of the histone code",
abstract = "Dynamic posttranslational modification of serine and threonine residues of nucleocytoplasmic proteins by β-N-acetylglucosamine (O-GlcNAc) is a regulator of cellular processes such as transcription, signaling, and protein-protein interactions. Like phosphorylation, O-GlcNAc cycles in response to a wide variety of stimuli. Although cycling of O-GlcNAc is catalyzed by only two highly conserved enzymes, O-GlcNAc transferase (OGT), which adds the sugar, and β-N-acetylglucosaminidase (O-GlcNAcase), which hydrolyzes it, the targeting of these enzymes is highly specific and is controlled by myriad interacting subunits. Here, we demonstrate by multiple specific immunological and enzymatic approaches that histones, the proteins that package DNA within the nucleus, are O-GlcNAcylated in vivo. Histones also are substrates for OGT in vitro. We identify O-GlcNAc sites on histones H2A, H2B, and H4 using mass spectrometry. Finally, we show that histone O-GlcNAcylation changes during mitosis and with heat shock. Taken together, these data show that O-GlcNAc cycles dynamically on histones and can be considered part of the histone code.",
keywords = "Epigenetics, Histones",
author = "Kaoru Sakabe and Zihao Wang and Hart, {Gerald Warren}",
year = "2010",
month = "11",
day = "16",
doi = "10.1073/pnas.1009023107",
language = "English (US)",
volume = "107",
pages = "19915--19920",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "46",

}

TY - JOUR

T1 - β-N-acetylglucosamine (O-GlcNAc) is part of the histone code

AU - Sakabe, Kaoru

AU - Wang, Zihao

AU - Hart, Gerald Warren

PY - 2010/11/16

Y1 - 2010/11/16

N2 - Dynamic posttranslational modification of serine and threonine residues of nucleocytoplasmic proteins by β-N-acetylglucosamine (O-GlcNAc) is a regulator of cellular processes such as transcription, signaling, and protein-protein interactions. Like phosphorylation, O-GlcNAc cycles in response to a wide variety of stimuli. Although cycling of O-GlcNAc is catalyzed by only two highly conserved enzymes, O-GlcNAc transferase (OGT), which adds the sugar, and β-N-acetylglucosaminidase (O-GlcNAcase), which hydrolyzes it, the targeting of these enzymes is highly specific and is controlled by myriad interacting subunits. Here, we demonstrate by multiple specific immunological and enzymatic approaches that histones, the proteins that package DNA within the nucleus, are O-GlcNAcylated in vivo. Histones also are substrates for OGT in vitro. We identify O-GlcNAc sites on histones H2A, H2B, and H4 using mass spectrometry. Finally, we show that histone O-GlcNAcylation changes during mitosis and with heat shock. Taken together, these data show that O-GlcNAc cycles dynamically on histones and can be considered part of the histone code.

AB - Dynamic posttranslational modification of serine and threonine residues of nucleocytoplasmic proteins by β-N-acetylglucosamine (O-GlcNAc) is a regulator of cellular processes such as transcription, signaling, and protein-protein interactions. Like phosphorylation, O-GlcNAc cycles in response to a wide variety of stimuli. Although cycling of O-GlcNAc is catalyzed by only two highly conserved enzymes, O-GlcNAc transferase (OGT), which adds the sugar, and β-N-acetylglucosaminidase (O-GlcNAcase), which hydrolyzes it, the targeting of these enzymes is highly specific and is controlled by myriad interacting subunits. Here, we demonstrate by multiple specific immunological and enzymatic approaches that histones, the proteins that package DNA within the nucleus, are O-GlcNAcylated in vivo. Histones also are substrates for OGT in vitro. We identify O-GlcNAc sites on histones H2A, H2B, and H4 using mass spectrometry. Finally, we show that histone O-GlcNAcylation changes during mitosis and with heat shock. Taken together, these data show that O-GlcNAc cycles dynamically on histones and can be considered part of the histone code.

KW - Epigenetics

KW - Histones

UR - http://www.scopus.com/inward/record.url?scp=78650447665&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650447665&partnerID=8YFLogxK

U2 - 10.1073/pnas.1009023107

DO - 10.1073/pnas.1009023107

M3 - Article

VL - 107

SP - 19915

EP - 19920

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 46

ER -