达普
乙酰化
组蛋白
组蛋白H4
SAP30型
P300-CBP转录因子
生物化学
化学
细胞生物学
生物
组蛋白H2A
分子生物学
组蛋白乙酰转移酶
DNA
酶
基因
作者
Jiaojiao Zhang,Tingting Fan,Yun-Zi Mao,Jun‐Li Hou,Meng Wang,Min Zhang,Yan Lin,Lei Zhang,Guoquan Yan,Yanpeng An,Jun Yao,Cheng Zhang,Peng‐Cheng Lin,Yiyuan Yuan,Jian‐Yuan Zhao,Wei Xu,Shimin Zhao
标识
DOI:10.1038/s42255-021-00405-8
摘要
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. Zhang et al. identify a nuclear role for the glycolytic enzyme TPI1 in connecting nutrient status and cell cycle status to global histone acetylation.
科研通智能强力驱动
Strongly Powered by AbleSci AI