AMPK regulates histone H2B O-GlcNAcylation

Qiuran Xu; Caihong Yang; Yu Du; Yali Chen; Hailong Liu; Min Deng; Haoxing Zhang; Lei Zhang; Tongzheng Liu; Qingguang Liu; Liewei Wang; Zhenkun Lou; Huadong Pei

doi:10.1093/nar/gku236

AMPK regulates histone H2B O-GlcNAcylation

Qiuran Xu, Caihong Yang, Yu Du, Yali Chen, Hailong Liu, Min Deng, Haoxing Zhang, Lei Zhang, Tongzheng Liu, Qingguang Liu, Liewei Wang, Zhenkun Lou, Huadong Pei

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

46 Scopus citations

Abstract

Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. However, how this epigenetic modification is regulated remains unclear. Here we found that the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) could suppress histone H2B O-GlcNAcylation. AMPK directly phosphorylates O-linked -N-acetylglucosamine (O-GlcNAc) transferase (OGT). Although this phosphorylation does not regulate the enzymatic activity of OGT, it inhibits OGT-chromatin association, histone O-GlcNAcylation and gene transcription. Conversely, OGT also O-GlcNAcylates AMPK and positively regulates AMPK activity, creating a feedback loop. Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription.

Original language	English (US)
Pages (from-to)	5594-5604
Number of pages	11
Journal	Nucleic acids research
Volume	42
Issue number	9
DOIs	https://doi.org/10.1093/nar/gku236
State	Published - May 2014

ASJC Scopus subject areas

Genetics

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title = "AMPK regulates histone H2B O-GlcNAcylation",

abstract = "Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. However, how this epigenetic modification is regulated remains unclear. Here we found that the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) could suppress histone H2B O-GlcNAcylation. AMPK directly phosphorylates O-linked -N-acetylglucosamine (O-GlcNAc) transferase (OGT). Although this phosphorylation does not regulate the enzymatic activity of OGT, it inhibits OGT-chromatin association, histone O-GlcNAcylation and gene transcription. Conversely, OGT also O-GlcNAcylates AMPK and positively regulates AMPK activity, creating a feedback loop. Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription.",

author = "Qiuran Xu and Caihong Yang and Yu Du and Yali Chen and Hailong Liu and Min Deng and Haoxing Zhang and Lei Zhang and Tongzheng Liu and Qingguang Liu and Liewei Wang and Zhenkun Lou and Huadong Pei",

year = "2014",

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doi = "10.1093/nar/gku236",

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TY - JOUR

T1 - AMPK regulates histone H2B O-GlcNAcylation

AU - Xu, Qiuran

AU - Yang, Caihong

AU - Du, Yu

AU - Chen, Yali

AU - Liu, Hailong

AU - Deng, Min

AU - Zhang, Haoxing

AU - Zhang, Lei

AU - Liu, Tongzheng

AU - Liu, Qingguang

AU - Wang, Liewei

AU - Lou, Zhenkun

AU - Pei, Huadong

PY - 2014/5

Y1 - 2014/5

N2 - Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. However, how this epigenetic modification is regulated remains unclear. Here we found that the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) could suppress histone H2B O-GlcNAcylation. AMPK directly phosphorylates O-linked -N-acetylglucosamine (O-GlcNAc) transferase (OGT). Although this phosphorylation does not regulate the enzymatic activity of OGT, it inhibits OGT-chromatin association, histone O-GlcNAcylation and gene transcription. Conversely, OGT also O-GlcNAcylates AMPK and positively regulates AMPK activity, creating a feedback loop. Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription.

AB - Histone H2B O-GlcNAcylation is an important post-translational modification of chromatin during gene transcription. However, how this epigenetic modification is regulated remains unclear. Here we found that the energy-sensing adenosine-monophosphate-activated protein kinase (AMPK) could suppress histone H2B O-GlcNAcylation. AMPK directly phosphorylates O-linked -N-acetylglucosamine (O-GlcNAc) transferase (OGT). Although this phosphorylation does not regulate the enzymatic activity of OGT, it inhibits OGT-chromatin association, histone O-GlcNAcylation and gene transcription. Conversely, OGT also O-GlcNAcylates AMPK and positively regulates AMPK activity, creating a feedback loop. Taken together, these results reveal a crosstalk between the LKB1-AMPK and the hexosamine biosynthesis (HBP)-OGT pathways, which coordinate together for the sensing of nutrient state and regulation of gene transcription.

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DO - 10.1093/nar/gku236

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SP - 5594

EP - 5604

JO - Nucleic acids research

JF - Nucleic acids research

IS - 9

ER -

AMPK regulates histone H2B O-GlcNAcylation

Abstract

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