Nuclear dihydroxyacetone phosphate signals nutrient sufficiency and cell cycle phase to global histone acetylation

Jiao Jiao Zhang; Ting Ting Fan; Yun Zi Mao; Jun Li Hou; Meng Wang; Min Zhang; Yan Lin; Lei Zhang; Guo Quan Yan; Yan Peng An; Jun Yao; Cheng Zhang; Peng Cheng Lin; Yi Yuan Yuan; Jian Yuan Zhao; Wei Xu; Shi Min Zhao

doi:10.1038/s42255-021-00405-8

Nuclear dihydroxyacetone phosphate signals nutrient sufficiency and cell cycle phase to global histone acetylation

Jiao Jiao Zhang, Ting Ting Fan, Yun Zi Mao, Jun Li Hou, Meng Wang, Min Zhang, Yan Lin, Lei Zhang, Guo Quan Yan, Yan Peng An, Jun Yao, Cheng Zhang, Peng Cheng Lin, Yi Yuan Yuan, Jian Yuan Zhao, Wei Xu, Shi Min Zhao

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

34 Scopus citations

Abstract

Global histone acetylation varies with changes in the nutrient and cell cycle phases; however, the mechanisms connecting these variations are not fully understood. Herein, we report that nutrient-related and cell-cycle-regulated nuclear acetate regulates global histone acetylation. Histone deacetylation-generated acetate accumulates in the nucleus and induces histone hyperacetylation. The nuclear acetate levels were controlled by glycolytic enzyme triosephosphate isomerase 1 (TPI1). Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. CDK2 accumulates in the cytosol during the late G1/S phases. Inactivation or blockade of nuclear translocation of TPI1 abrogates nutrient-dependent and cell-cycle-dependent global histone acetylation, chromatin condensation, gene transcription and DNA replication. These results identify the mechanism of maintaining global histone acetylation by nutrient and cell cycle signals.

Original language	English
Pages (from-to)	859-875
Number of pages	17
Journal	Nature Metabolism
Volume	3
Issue number	6
DOIs	https://doi.org/10.1038/s42255-021-00405-8
State	Published - Jun 2021
Externally published	Yes

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Zhang, J. J., Fan, T. T., Mao, Y. Z., Hou, J. L., Wang, M., Zhang, M., Lin, Y., Zhang, L., Yan, G. Q., An, Y. P., Yao, J., Zhang, C., Lin, P. C., Yuan, Y. Y., Zhao, J. Y., Xu, W., & Zhao, S. M. (2021). Nuclear dihydroxyacetone phosphate signals nutrient sufficiency and cell cycle phase to global histone acetylation. Nature Metabolism, 3(6), 859-875. https://doi.org/10.1038/s42255-021-00405-8

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title = "Nuclear dihydroxyacetone phosphate signals nutrient sufficiency and cell cycle phase to global histone acetylation",

abstract = "Global histone acetylation varies with changes in the nutrient and cell cycle phases; however, the mechanisms connecting these variations are not fully understood. Herein, we report that nutrient-related and cell-cycle-regulated nuclear acetate regulates global histone acetylation. Histone deacetylation-generated acetate accumulates in the nucleus and induces histone hyperacetylation. The nuclear acetate levels were controlled by glycolytic enzyme triosephosphate isomerase 1 (TPI1). Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. CDK2 accumulates in the cytosol during the late G1/S phases. Inactivation or blockade of nuclear translocation of TPI1 abrogates nutrient-dependent and cell-cycle-dependent global histone acetylation, chromatin condensation, gene transcription and DNA replication. These results identify the mechanism of maintaining global histone acetylation by nutrient and cell cycle signals.",

author = "Zhang, \{Jiao Jiao\} and Fan, \{Ting Ting\} and Mao, \{Yun Zi\} and Hou, \{Jun Li\} and Meng Wang and Min Zhang and Yan Lin and Lei Zhang and Yan, \{Guo Quan\} and An, \{Yan Peng\} and Jun Yao and Cheng Zhang and Lin, \{Peng Cheng\} and Yuan, \{Yi Yuan\} and Zhao, \{Jian Yuan\} and Wei Xu and Zhao, \{Shi Min\}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = jun,

doi = "10.1038/s42255-021-00405-8",

language = "英语",

volume = "3",

pages = "859--875",

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T1 - Nuclear dihydroxyacetone phosphate signals nutrient sufficiency and cell cycle phase to global histone acetylation

AU - Zhang, Jiao Jiao

AU - Fan, Ting Ting

AU - Mao, Yun Zi

AU - Hou, Jun Li

AU - Wang, Meng

AU - Zhang, Min

AU - Lin, Yan

AU - Zhang, Lei

AU - Yan, Guo Quan

AU - An, Yan Peng

AU - Yao, Jun

AU - Zhang, Cheng

AU - Lin, Peng Cheng

AU - Yuan, Yi Yuan

AU - Zhao, Jian Yuan

AU - Xu, Wei

AU - Zhao, Shi Min

PY - 2021/6

Y1 - 2021/6

N2 - Global histone acetylation varies with changes in the nutrient and cell cycle phases; however, the mechanisms connecting these variations are not fully understood. Herein, we report that nutrient-related and cell-cycle-regulated nuclear acetate regulates global histone acetylation. Histone deacetylation-generated acetate accumulates in the nucleus and induces histone hyperacetylation. The nuclear acetate levels were controlled by glycolytic enzyme triosephosphate isomerase 1 (TPI1). Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. CDK2 accumulates in the cytosol during the late G1/S phases. Inactivation or blockade of nuclear translocation of TPI1 abrogates nutrient-dependent and cell-cycle-dependent global histone acetylation, chromatin condensation, gene transcription and DNA replication. These results identify the mechanism of maintaining global histone acetylation by nutrient and cell cycle signals.

AB - Global histone acetylation varies with changes in the nutrient and cell cycle phases; however, the mechanisms connecting these variations are not fully understood. Herein, we report that nutrient-related and cell-cycle-regulated nuclear acetate regulates global histone acetylation. Histone deacetylation-generated acetate accumulates in the nucleus and induces histone hyperacetylation. The nuclear acetate levels were controlled by glycolytic enzyme triosephosphate isomerase 1 (TPI1). Cyclin-dependent kinase 2 (CDK2), which is phosphorylated and activated by nutrient-activated mTORC1, phosphorylates TPI1 Ser 117 and promotes nuclear translocation of TPI1, decreases nuclear dihydroxyacetone phosphate (DHAP) and induces nuclear acetate accumulation because DHAP scavenges acetate via the formation of 1-acetyl-DHAP. CDK2 accumulates in the cytosol during the late G1/S phases. Inactivation or blockade of nuclear translocation of TPI1 abrogates nutrient-dependent and cell-cycle-dependent global histone acetylation, chromatin condensation, gene transcription and DNA replication. These results identify the mechanism of maintaining global histone acetylation by nutrient and cell cycle signals.

UR - https://www.scopus.com/pages/publications/85108116195

U2 - 10.1038/s42255-021-00405-8

DO - 10.1038/s42255-021-00405-8

M3 - 文章

C2 - 34140692

AN - SCOPUS:85108116195

SN - 2522-5812

VL - 3

SP - 859

EP - 875

JO - Nature Metabolism

JF - Nature Metabolism

IS - 6

ER -

Nuclear dihydroxyacetone phosphate signals nutrient sufficiency and cell cycle phase to global histone acetylation

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