High areal capacity is one of the critically important points for potassium-ion batteries(PIBs)for practical applications,which relies on high areal-massloading electrodes operating at high reversible capacity.However...High areal capacity is one of the critically important points for potassium-ion batteries(PIBs)for practical applications,which relies on high areal-massloading electrodes operating at high reversible capacity.However,it is remarkably restricted by the mechanical instability and sluggish charge transfer induced by the increased mass loading.To overcome such challenge,we report the rationally designed bimetallic selenides CoSe2/SnSe2 heterostructures confined in hierarchical carbon nanofibers(CSSe@CNFs),which enables the electrodes robust mechanical stability,enhanced electron transport,and reduced ion-diffusion energy barrier for facilitating reaction kinetics.Accordingly,an impressive areal mass loading up to 25.3 mg cm^(−2)was achieved,which endowed a high areal capacity of 7.58 mAh cm^(−2)for such a free-standing electrode.This is stateof-the-art among the PIBs,exceeding that of today’s industry standard(∼3 mAh cm^(−2)for LIBs).Furthermore,it delivered long-term stability over 3700 cycles at high current density(∼2 mA cm^(−2),vs 1 mA cm^(−2)in LIBs).Moreover,the as-constructed full battery achieved a high energy density of 172.8 Wh kg-1 at 0.05 A g^(−1)with a satisfied cycle stability over 2000 cycles at 2 A g^(−1)and high reversibility with Coulombic efficiency of 100%;thus,signifying its bright future toward commercial application for advanced PIBs.展开更多
Pervasive transcription of the mammalian genome produces hundreds of thousands of noncoding RNAs(ncRNAs).Numerous studies have suggested that some of these ncRNAs regulate multiple cellular processes and play importan...Pervasive transcription of the mammalian genome produces hundreds of thousands of noncoding RNAs(ncRNAs).Numerous studies have suggested that some of these ncRNAs regulate multiple cellular processes and play important roles in physiological and pathological processes.Notably,a large subset of ncRNAs is enriched on chromatin and participates in regulating gene expression and the dynamics of chromatin structure and status.In this review,we summarize recent advances in the functional study of chromatin-associated ncRNAs and mechanistic insights into how these ncRNAs associate with chromatin.We also discuss the potential future challenges which still need to be overcome in this field.展开更多
LIN28 is an RNA binding protein with important roles in early embryo development,stem cell differentiation/re-programming,tumorigenesis and metabolism.Previous studies have focused mainly on its role in the cytosol wh...LIN28 is an RNA binding protein with important roles in early embryo development,stem cell differentiation/re-programming,tumorigenesis and metabolism.Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs,and few have addressed LIN28's role within the nucleus.Here,we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development.Maternal LIN28 expression drops upon exit from the 2-cell stage,and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blas-tocyst stage development,to become dominantly expressed in the cytosol after implantation.In cultured pluripotent stem cells(PSCs),loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes.Mechanistically,LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity,and its loss leads to nucleolar phase separation defects,ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux.LIN28 also resides in a complex containing the nucleolar factor Nucleolin(NCL)and the transcrip-tional repressor TRIM28,and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci,and thus de-repressed Dux and reduced rRNA expression.Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling,translationally inert and anabolically inactive state,which is a part of previously unappreciated 2C-like transcriptional program.These findings elucidate novel roles for nucleolar LIN28 in PSCs,and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.展开更多
The metabolic enzyme isocitrate dehydrogenase 1(IDH1)catalyzes the oxidative decarboxylation of isocitrate to a-ketoglutarate(a-KG).Its mutation often leads to aberrant gene expression in cancer.IDH1 was reported to b...The metabolic enzyme isocitrate dehydrogenase 1(IDH1)catalyzes the oxidative decarboxylation of isocitrate to a-ketoglutarate(a-KG).Its mutation often leads to aberrant gene expression in cancer.IDH1 was reported to bind thousands of RNA transcripts in a sequence-dependent manner;yet,the functional significance of this RNA-binding activity remains elusive.Here,we report that IDH1 promotes mRNA translation via direct associations with polysome mRNA and translation machinery.Comprehensive proteomic analysis in embryonic stem cells(ESCs)revealed strikingenrichmentof ribosomal proteins and translation regulators in IDH1-bound protein interactomes.We performed ribosomal profiling and analyzed mRNA transcripts that are associated with actively translating polysomes.Interestingly,knockout of IDH1 in ESCs led to significant downregulation of polysome-bound mRNA in IDH1 targets and subtle upregulation of ribosome densities at the start codon,indicating inefficient translation initiation upon loss of IDH1.Tethering IDH1 to a luciferase mRNA via the MS2-MBP system promotes luciferase translation,independently of the catalytic activity of IDH1.Intriguingly,IDH1 fails to enhance luciferase translation driven by an internal ribosome entry site.Together,these results reveal an unforeseen role of IDH1 in fine-tuning cap-dependent translation via the initiation step.展开更多
Super-enhancers(SEs)comprise large clusters of enhancers,which are co-occupied by multiple lineage-specific and master tran-scription factors,and play pivotal roles in regulating gene expression and cell fate determin...Super-enhancers(SEs)comprise large clusters of enhancers,which are co-occupied by multiple lineage-specific and master tran-scription factors,and play pivotal roles in regulating gene expression and cell fate determination.However,it is still largely un-known whether and how SEs are regulated by the noncoding portion of the genome.Here,through genome-wide analysis,wefound that tpng noncoding RNA(IncRNA)genes preferentially lie next to SEs.In mouse embryonic stem cells(mESCs),depletionof$E-associated IlncRNA transcripts dysregulated the activity of their nearby SEs.Specifically,we revealed a critical regulatoryrole of the IncRNA gene Platr22 in modulating the activity of a nearby SE and the expression of the nearby pluripotency regulatorZFP281.Through these regulatory events,Platr22 contributes to pluripotency maintenance and proper differentiation of mESCs.Mechanistically,Platr22 transcripts coat chromatin near the SE region and interact with DDX5 and hnRNP-L.DDX5 further recruitsp300 and other factors related to active transcription.We propose that these factors assemble into a transcription hub,thus pro-moting an open and active epigenetic chromatin state.0ur study highlights an unanticipated role for a class of lncRNAs in epige-netically controlling the activity and vulnerability to perturbation of nearby SEs for cell fate determination.展开更多
There is an increasing interest in understanding how three-dimensional(3D)organization of the genome is regulated.Different strategies have been employed to identify genome-wide chromatin interactions.However,due to c...There is an increasing interest in understanding how three-dimensional(3D)organization of the genome is regulated.Different strategies have been employed to identify genome-wide chromatin interactions.However,due to current limitations in resolving genomic contacts,visualization and validation of these genomic loci with sub-kilobase resolution remain unsolved to date.Here,we describe Tn5 transposase-based Fluorescencein situhybridization(Tn5-FISH),a PCR-based,cost-effective imaging method,which can co-localize the genomic loci with sub-kilobase resolution,dissect genome architecture,and verify chromatin interactions detected by chromatin configuration capture(3C)-derived methods.To validate this method,short-range interactions in keratin-encoding gene(KRT)locus in topologically associated domain(TAD)were imaged by triple-color Tn5-FISH,indicating that Tn5-FISH is very useful to verify short-range chromatin interactions inside the contact domain and TAD.Therefore,Tn5-FISH can be a powerful molecular tool for the clinical detection of cytogenetic changes in numerous genetic diseases such as cancers.展开更多
基金supported by the National Natural Science Foundation of China(grant nos.52074113,22005091,and 22005092)the Hunan University Outstanding Youth Science Foundation(grant no.531118040319).
文摘High areal capacity is one of the critically important points for potassium-ion batteries(PIBs)for practical applications,which relies on high areal-massloading electrodes operating at high reversible capacity.However,it is remarkably restricted by the mechanical instability and sluggish charge transfer induced by the increased mass loading.To overcome such challenge,we report the rationally designed bimetallic selenides CoSe2/SnSe2 heterostructures confined in hierarchical carbon nanofibers(CSSe@CNFs),which enables the electrodes robust mechanical stability,enhanced electron transport,and reduced ion-diffusion energy barrier for facilitating reaction kinetics.Accordingly,an impressive areal mass loading up to 25.3 mg cm^(−2)was achieved,which endowed a high areal capacity of 7.58 mAh cm^(−2)for such a free-standing electrode.This is stateof-the-art among the PIBs,exceeding that of today’s industry standard(∼3 mAh cm^(−2)for LIBs).Furthermore,it delivered long-term stability over 3700 cycles at high current density(∼2 mA cm^(−2),vs 1 mA cm^(−2)in LIBs).Moreover,the as-constructed full battery achieved a high energy density of 172.8 Wh kg-1 at 0.05 A g^(−1)with a satisfied cycle stability over 2000 cycles at 2 A g^(−1)and high reversibility with Coulombic efficiency of 100%;thus,signifying its bright future toward commercial application for advanced PIBs.
基金the National Natural Science Foundation of China(31925015,32122019,32270582).
文摘Pervasive transcription of the mammalian genome produces hundreds of thousands of noncoding RNAs(ncRNAs).Numerous studies have suggested that some of these ncRNAs regulate multiple cellular processes and play important roles in physiological and pathological processes.Notably,a large subset of ncRNAs is enriched on chromatin and participates in regulating gene expression and the dynamics of chromatin structure and status.In this review,we summarize recent advances in the functional study of chromatin-associated ncRNAs and mechanistic insights into how these ncRNAs associate with chromatin.We also discuss the potential future challenges which still need to be overcome in this field.
基金We thank Hengyu Fan,Dan Zhang,Jianzhong Sheng,Pengfei Xu and Hua Lu for discussing and sharing facilities.J.Z.is supported by the National Key Research and Development Program of China(2018YFA0107100,2018YFA0107103,2018YFC1005002)the National Natural Science Foundation projects of China(31871453,91857116)+3 种基金the Zhejiang Natural Science Foundation projects of China(LR19C120001)High-Performance Computing Platform in Center of Cryo-Electron Microscopy of Zhejiang University and core facilities,Zhejiang University School of Medicine.H.Y.is supported by the Zhejiang Natural Science Foundation Projects of China(Grant No.LQ21C120002)J.W.is supported by National Institutes of Health(HD097268)New York State Stem Cell Science(C32569GG).
文摘LIN28 is an RNA binding protein with important roles in early embryo development,stem cell differentiation/re-programming,tumorigenesis and metabolism.Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs,and few have addressed LIN28's role within the nucleus.Here,we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development.Maternal LIN28 expression drops upon exit from the 2-cell stage,and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blas-tocyst stage development,to become dominantly expressed in the cytosol after implantation.In cultured pluripotent stem cells(PSCs),loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes.Mechanistically,LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity,and its loss leads to nucleolar phase separation defects,ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux.LIN28 also resides in a complex containing the nucleolar factor Nucleolin(NCL)and the transcrip-tional repressor TRIM28,and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci,and thus de-repressed Dux and reduced rRNA expression.Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling,translationally inert and anabolically inactive state,which is a part of previously unappreciated 2C-like transcriptional program.These findings elucidate novel roles for nucleolar LIN28 in PSCs,and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
基金This work was supported in part by the National Natural Science Foundation of China(31471219 and 31630095)the National Basic Research Program of China(2017YFA0504204)the Center for Life Sciences at Tsinghua University.
文摘The metabolic enzyme isocitrate dehydrogenase 1(IDH1)catalyzes the oxidative decarboxylation of isocitrate to a-ketoglutarate(a-KG).Its mutation often leads to aberrant gene expression in cancer.IDH1 was reported to bind thousands of RNA transcripts in a sequence-dependent manner;yet,the functional significance of this RNA-binding activity remains elusive.Here,we report that IDH1 promotes mRNA translation via direct associations with polysome mRNA and translation machinery.Comprehensive proteomic analysis in embryonic stem cells(ESCs)revealed strikingenrichmentof ribosomal proteins and translation regulators in IDH1-bound protein interactomes.We performed ribosomal profiling and analyzed mRNA transcripts that are associated with actively translating polysomes.Interestingly,knockout of IDH1 in ESCs led to significant downregulation of polysome-bound mRNA in IDH1 targets and subtle upregulation of ribosome densities at the start codon,indicating inefficient translation initiation upon loss of IDH1.Tethering IDH1 to a luciferase mRNA via the MS2-MBP system promotes luciferase translation,independently of the catalytic activity of IDH1.Intriguingly,IDH1 fails to enhance luciferase translation driven by an internal ribosome entry site.Together,these results reveal an unforeseen role of IDH1 in fine-tuning cap-dependent translation via the initiation step.
基金Grant support is from the National Basic Research Program of China(2017YFA050420A and 2018YFA0107604)the National Natural Science Foundation of China(31630095 and 31925015)+1 种基金the Center for Life Science at Tsinghua UniversityWe thank J.Wang,X.Fu,B.Zhou,and Shen laboratory members for insightful discussion and suggestions.
文摘Super-enhancers(SEs)comprise large clusters of enhancers,which are co-occupied by multiple lineage-specific and master tran-scription factors,and play pivotal roles in regulating gene expression and cell fate determination.However,it is still largely un-known whether and how SEs are regulated by the noncoding portion of the genome.Here,through genome-wide analysis,wefound that tpng noncoding RNA(IncRNA)genes preferentially lie next to SEs.In mouse embryonic stem cells(mESCs),depletionof$E-associated IlncRNA transcripts dysregulated the activity of their nearby SEs.Specifically,we revealed a critical regulatoryrole of the IncRNA gene Platr22 in modulating the activity of a nearby SE and the expression of the nearby pluripotency regulatorZFP281.Through these regulatory events,Platr22 contributes to pluripotency maintenance and proper differentiation of mESCs.Mechanistically,Platr22 transcripts coat chromatin near the SE region and interact with DDX5 and hnRNP-L.DDX5 further recruitsp300 and other factors related to active transcription.We propose that these factors assemble into a transcription hub,thus pro-moting an open and active epigenetic chromatin state.0ur study highlights an unanticipated role for a class of lncRNAs in epige-netically controlling the activity and vulnerability to perturbation of nearby SEs for cell fate determination.
基金This work was supported in part by the State Key Research Development Program of China(2017YFA0505503)the National Natural Science Foundation of China(81890991 and 31671383)+4 种基金Beijing Advanced Innovation Center for Structural Bio logy,Tsinghua University(100300001)the fund from Foshan-Tsinghua Innovation Special Fund(FTISF,2019THFS0141)to J.G.,the National Natural Science Foundation of China(31871444)the program for Guangdong Introducing Innovative and Entrepreneurial Teams(2016ZT06S029)to J.W.Australia China Science and Research Fund Joint Research Centre for POCT(ACSRF65827)Shenzhen Science and Technology Program(KQTD 20170810110913065)to D.J.
文摘There is an increasing interest in understanding how three-dimensional(3D)organization of the genome is regulated.Different strategies have been employed to identify genome-wide chromatin interactions.However,due to current limitations in resolving genomic contacts,visualization and validation of these genomic loci with sub-kilobase resolution remain unsolved to date.Here,we describe Tn5 transposase-based Fluorescencein situhybridization(Tn5-FISH),a PCR-based,cost-effective imaging method,which can co-localize the genomic loci with sub-kilobase resolution,dissect genome architecture,and verify chromatin interactions detected by chromatin configuration capture(3C)-derived methods.To validate this method,short-range interactions in keratin-encoding gene(KRT)locus in topologically associated domain(TAD)were imaged by triple-color Tn5-FISH,indicating that Tn5-FISH is very useful to verify short-range chromatin interactions inside the contact domain and TAD.Therefore,Tn5-FISH can be a powerful molecular tool for the clinical detection of cytogenetic changes in numerous genetic diseases such as cancers.