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 β-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.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Qiuran
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Du
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Haoxing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Tongzheng
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Qingguang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA peihuadong@126.com.
authors.forename: Liewei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA peihuadong@126.com.
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Lou
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China peihuadong@126.com.
authors.forename: Huadong
authors.initials: H
authors.lastname: Pei
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000117:Acetylglucosamine / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004734:Energy Metabolism; D044127:Epigenesis, Genetic; D006031:Glycosylation; D056945:Hep G2 Cells; D006657:Histones / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones; D017351:N-Acetylglucosaminyltransferases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; D000117:Acetylglucosamine