Dear Editor,Similar to higher-order folding of polypeptide chains into functional proteins,linear DNA molecules are spatially folded in a hierarchical and dynamic manner into three-dimensional(3D)functional chromatin ...Dear Editor,Similar to higher-order folding of polypeptide chains into functional proteins,linear DNA molecules are spatially folded in a hierarchical and dynamic manner into three-dimensional(3D)functional chromatin structures in eukaryotic nuclei(Huang and Wu,2016;Rowley and Corces,2018).This dynamic folding is closely related to many nuclear processes such as DNA replication and repair,chromosomal translocation,recombination,and segregation,as well as RNA transcription,splicing,and transport.In particular,dynamic long-distance chromatin looping interactions,which result in close spatial contacts between distal enhancers and target promoters,are thought to play a role in controlling precise spatiotemporal as well as cell-type specific gene expression during animal development(Rowley and Corces,2018).Mammalian genomes contain numerous noncoding regulatory elements that regulate these dynamic long-distance chromatin looping interactions.展开更多
In a tour-de-force study by Zhang et al.recently published in Nature Metabolism,a newly identified aldolase inhibitor,Aldometanib,is shown to activate lysosomal AMP-activated protein kinase(AMPK).Remarkably,mice treat...In a tour-de-force study by Zhang et al.recently published in Nature Metabolism,a newly identified aldolase inhibitor,Aldometanib,is shown to activate lysosomal AMP-activated protein kinase(AMPK).Remarkably,mice treated with Aldometanib have increased insulin sensitivity,lowered blood glucose,and decreased hepatic steatosis and fibrosis,and are long-lived,effects of which all appear to be mediated via activation of lysosomal AMPK.AMPK is a central regulator of mammalian energy homeostasis,and activation of AMPK regulates a wide range of biological processes that are linked to multiple health benefits,associated with an increased healthy lifespan[1].Designing efficacious AMPK activators for clinical use that show long-term safety profiles has proved challenging,but the potential reward for such drugs would be substantial.展开更多
基金This work was supported by Grants from MOST(2017YFA0504203,2018YFC1004504)the National Natural Science Foundation of China(31630039,91640118,and 31470820)to Q.W.Q.W.is a Shanghai Subject Chief Scientist.
文摘Dear Editor,Similar to higher-order folding of polypeptide chains into functional proteins,linear DNA molecules are spatially folded in a hierarchical and dynamic manner into three-dimensional(3D)functional chromatin structures in eukaryotic nuclei(Huang and Wu,2016;Rowley and Corces,2018).This dynamic folding is closely related to many nuclear processes such as DNA replication and repair,chromosomal translocation,recombination,and segregation,as well as RNA transcription,splicing,and transport.In particular,dynamic long-distance chromatin looping interactions,which result in close spatial contacts between distal enhancers and target promoters,are thought to play a role in controlling precise spatiotemporal as well as cell-type specific gene expression during animal development(Rowley and Corces,2018).Mammalian genomes contain numerous noncoding regulatory elements that regulate these dynamic long-distance chromatin looping interactions.
文摘In a tour-de-force study by Zhang et al.recently published in Nature Metabolism,a newly identified aldolase inhibitor,Aldometanib,is shown to activate lysosomal AMP-activated protein kinase(AMPK).Remarkably,mice treated with Aldometanib have increased insulin sensitivity,lowered blood glucose,and decreased hepatic steatosis and fibrosis,and are long-lived,effects of which all appear to be mediated via activation of lysosomal AMPK.AMPK is a central regulator of mammalian energy homeostasis,and activation of AMPK regulates a wide range of biological processes that are linked to multiple health benefits,associated with an increased healthy lifespan[1].Designing efficacious AMPK activators for clinical use that show long-term safety profiles has proved challenging,but the potential reward for such drugs would be substantial.
