As sessile organisms, plants encounter various environmental stimuli including abiotic stresses during their lifecycle. To survive under adverse conditions, plants have evolved intricate mechanisms to perceive externa...As sessile organisms, plants encounter various environmental stimuli including abiotic stresses during their lifecycle. To survive under adverse conditions, plants have evolved intricate mechanisms to perceive external signals and respond accordingly. Responses to various stresses largely depend on the plant capacity to modulate the transcriptome rapidly and specifically. A number of studies have shown that the molecular mechanisms driving the responses of plants to environmental stresses often depend on nucleosome histone post-translational modifications including histone acetylation, methylation, ubiquitination, and phosphorylation. The combined effects of these modifications play an essential role in the regulation of stress responsive gene expression. In this review, we highlight our current understanding of the epigenetic mechanisms of histone modifications and their roles in plant ahiotic stress response.展开更多
TP53 is the most frequently mutated gene across all cancer types. Our understanding of its functions has evolved since its discovery four decades ago. Initially thought to be an oncogene, it was later realized to be a...TP53 is the most frequently mutated gene across all cancer types. Our understanding of its functions has evolved since its discovery four decades ago. Initially thought to be an oncogene, it was later realized to be a critical tumour suppressor. A significant amount of our knowledge about p53 functions have come from the use of antibodies against its various forms. The early anti-p53 antibodies contributed to the recognition of p53 accumulation as a common feature of cancer cells and to our understanding of p53 DNA-binding and transcription activities. They led to the concept that conformational changes can facilitate p53’s activity as a growth inhibitory protein. The ensuing p53 conformational-specific antibodies further underlined p53’s conformational flexibility, collectively forming the basis for current efforts to generate therapeutic molecules capable of altering the conformation of mutant p53. A subsequent barrage of antibodies against post-translational modifications on p53 has clarified p53’s roles further, especially with respect to the mechanistic details and context-dependence of its activity. More recently, the generation of p53 mutation-specific antibodies have highlighted the possibility to go beyond the general framework of our comprehension of mutant p53-and promises to provide insights into the specific properties of individual p53 mutants. This review summarizes our current knowledge of p53 functions derived through the major classes of anti-p53 antibodies, which could be a paradigm for understanding other molecular events in health and disease.展开更多
Mammalian fertilization begins with the fusion of two specialized gametes,followed by major epigenetic remodeling leading to the formation of a totipotent embryo.During the development of the pre-implantation embryo,p...Mammalian fertilization begins with the fusion of two specialized gametes,followed by major epigenetic remodeling leading to the formation of a totipotent embryo.During the development of the pre-implantation embryo,precise reprogramming progress is a prerequisite for avoiding developmental defects or embryonic lethality,but the underlying molecular mechanisms remain elusive.For the past few years,unprecedented breakthroughs have been made in mapping the regulatory network of dynamic epigenomes during mammalian early embryo development,taking advantage of multiple advances and innovations in low-input genome-wide chromatin analysis technologies.The aim of this review is to highlight the most recent progress in understanding the mechanisms of epigenetic remodeling during early embryogenesis in mammals,including DNA methylation,histone modifications,chromatin accessibility and 3D chromatin organization.展开更多
Although the molecular basis of flowering time control is well dissected in the long day （LD） plant Arabidopsis, it is still largely unknown in the short day （SD） plant rice. Rice flowering time （heading date） i...Although the molecular basis of flowering time control is well dissected in the long day （LD） plant Arabidopsis, it is still largely unknown in the short day （SD） plant rice. Rice flowering time （heading date） is an important agronomic trait for season adaption and grain yield, which is affected by both genetic and environmental factors. During the last decade, as the nature of florigen was identified, notable progress has been made on exploration how florigen gene ,expression is genetically controlled. In Arabidopsis expression of certain key flowering integrators such as FLOWERING LOCUS C （FLC） and FLOWERING LOCUS T （FT） are also epige- netically regulated by various chromatin modifications, however, very little is known in rice on this aspect until very recently. This review summarized the advances of both genetic networks and chromatin modifications in rice flowering time control, attempting to give a complete view of the genetic and epigenetic architecture in complex network of rice flowering pathways.展开更多
Infiammasomes play essential roles in immune protection against microbial infections. However, excessive inflammation is implicated in various human diseases, including autoinflammatory syndromes, diabetes, multiple s...Infiammasomes play essential roles in immune protection against microbial infections. However, excessive inflammation is implicated in various human diseases, including autoinflammatory syndromes, diabetes, multiple sclerosis, cardiovascular disorders and neurodegenerative diseases. Therefore, precise regulation of inflammasome activities is critical for adequate immune protection while limiting collateral tissue damage. In this review, we focus on the emerging roles of post-translational modifications （PTMs） that regulate activation of the NLRP3, NLRP1, NLRC4, AIM2 and IFI16 inflammasomes. We anticipate that these types of PTMs will be identified in other types of and less well-characterized inflammasomes. Because these highly diverse and versatile PTMs shape distinct inflammatory responses in response to infections and tissue damage, targeting the enzymes involved in these PTMs will undoubtedly offer opportunities for precise modulation of inflammasome activities under various pathophysiological conditions.展开更多
Epigenetics refers to the study of heritable changes in gene function that do not involve changes in the DNA sequence. Such effects on cellular and physiological phenotypic traits may result from external or environme...Epigenetics refers to the study of heritable changes in gene function that do not involve changes in the DNA sequence. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors or be part of normal developmental program. In eukaryotes, DNA wraps on a histone octamer(two copies of H2A, H2B, H3 and H4) to form nucleosome, the fundamental unit of chromatin. The structure of chromatin is subjected to a dynamic regulation through multiple epigenetic mechanisms, including DNA methylation, histone posttranslational modifications(PTMs), chromatin remodeling and noncoding RNAs. As conserved regulatory mechanisms in gene expression, epigenetic mechanisms participate in almost all the important biological processes ranging from basal development to environmental response. Importantly, all of the major epigenetic mechanisms in mammalians also occur in plants. Plant studies have provided numerous important contributions to the epigenetic research. For example, gene imprinting, a mechanism of parental allele-specific gene expression, was firstly observed in maize; evidence of paramutation, an epigenetic phenomenon that one allele acts in a single locus to induce a heritable change in the other allele, was firstly reported in maize and tomato.Moreover, some unique epigenetic mechanisms have been evolved in plants. For example, the 24-nt siRNA-involved RNA-directed DNA methylation(RdDM) pathway is plant-specific because of the involvements of two plant-specific DNA-dependent RNA polymerases, Pol IV and Pol V. A thorough study of epigenetic mechanisms is of great significance to improve crop agronomic traits and environmental adaptability. In this review, we make a brief summary of important progress achieved in plant epigenetics field in China over the past several decades and give a brief outlook on future research prospects.We focus our review on DNA methylation and histone PTMs, the two most important aspects of epigenetic mechanisms.展开更多
聚乳酸( PLA)具有独特的可生物降解性和生物相容性,是一种理想的 3D 打印材料。3D 打印 PLA 材料应用广泛,特别是在生物医用领域。然而,PLA 也存在着一些性能缺陷,在一定程度上限制了其在 3D 打印上的应用,因此需要对 PLA 进行改性。文...聚乳酸( PLA)具有独特的可生物降解性和生物相容性,是一种理想的 3D 打印材料。3D 打印 PLA 材料应用广泛,特别是在生物医用领域。然而,PLA 也存在着一些性能缺陷,在一定程度上限制了其在 3D 打印上的应用,因此需要对 PLA 进行改性。文章首先分析了 PLA 作为 3D 打印材料存在脆性大、耐热性差和易水解的性能缺陷;其次综述了 3D 打印 PLA 的改性方法,包括共聚改性、表面改性和共混改性;然后介绍了 3D 打印 PLA 材料的应用领域,包括生物医学领域和工业制造领域。最后文章介绍了具有优异耐热性和耐水解性的生物降解型立构聚乳酸,并对立构聚乳酸作为 3D 打印材料的前景进行了展望。展开更多
Alcohol consumption causes cellular injury. Recent developments indicate that ethanol induces epigenetic alterations, particularly acetylation, methylation of histones, and hypo- and hypermethylation of DNA. This has ...Alcohol consumption causes cellular injury. Recent developments indicate that ethanol induces epigenetic alterations, particularly acetylation, methylation of histones, and hypo- and hypermethylation of DNA. This has opened up a new area of interest in ethanol research and is providing novel insight into actions of ethanol at the nucleosomal level in relation to gene expression and patho-physiological consequences. The epigenetic effects are mainly attributable to ethanol metabolic stress (Emess), generated by the oxidative and non-oxidative metabolism of ethanol, and dysregulation of methionine metabolism. Epigenetic changes are important in ethanol-induced hepatic steatosis, fibrosis, carcinoma and gastrointestinal injury. This editorial highlights these new advances and its future potential.展开更多
Diabetes has become the epidemic of the 21 st century, and with over 90% patients with diabetes becoming at a risk of developing retinopathy, diabetic retinopathy has emerged as a major public health concern. In spite...Diabetes has become the epidemic of the 21 st century, and with over 90% patients with diabetes becoming at a risk of developing retinopathy, diabetic retinopathy has emerged as a major public health concern. In spite of cutting edge research in the field, how retina and its vasculature are damaged by the diabetic milieu remains ambiguous. The environmental factors, life style or disease process can also bring in modifications in the DNA, and these epigenetic modifications either silence or activate a gene without altering the DNA sequence. Diabetic environment up- or downregulates a number of genes in the retina, and emerging research has shown that it also facilitates epigenetic modifications. In the pathogenesis of diabetic retinopathy, the genes associated with important enzymes(e.g., mitochondrial superoxide dismutase, matrix metalloproteinase-9 and thioredoxin interacting protein) and transcriptional factors are epigenetically modified, the enzymes responsible for these epigenetic modifications are either activated or inhibited, and the levels of micro RNAs are altered. With epigenetic modifications taking an important place in diabetic retinopathy, it is now becoming critical to evaluate these modifications, and understand their impact on this slow progressing blinding disease.展开更多
Inhibitors of protein deacetylases have recently been established as a novel therapeutic principle for several human diseases,including cancer.The original notion of the mechanism of action of these compounds focused ...Inhibitors of protein deacetylases have recently been established as a novel therapeutic principle for several human diseases,including cancer.The original notion of the mechanism of action of these compounds focused on the epigenetic control of transcriptional processes, especially of tumor suppressor genes,by interfering with the acetylation status of nuclear histone proteins,hence the name histone deacetylase inhibitors was coined.Yet,this view could not explain the high specificity for tumor cells and recent evidence now suggests that non-histone proteins represent major targets for protein deacetylase inhibitors and that the post-translational modification of the acetylome is involved in various cellular processes of differentiation,survival and cell death induction.展开更多
Pyruvate kinase isoform M2 （PKM2） converts phospho- enolpyruvate （PEP） to pyruvate and plays an important role in cancer metabolism. Here, we show that post- translational modifications and a patient-derived muta-...Pyruvate kinase isoform M2 （PKM2） converts phospho- enolpyruvate （PEP） to pyruvate and plays an important role in cancer metabolism. Here, we show that post- translational modifications and a patient-derived muta- tion regulate pyruvate kinase activity of PKM2 through modulating the conformation of the PKM2 tetramer. We determined crystal structures of human PKM2 mutants and proposed a ＂seesaw＂ model to illustrate confor- mational changes between an inactive T-state and an active R-state tetramers of PKM2. Biochemical and structural analyses demonstrate that PKM2^Y105E （phos- phorylation mimic of Y105） decreases pyruvate kinase activity by inhibiting FBP （fructose 1,6-bisphosphate）- induced R-state formation, and PKM2K^3305Q （acetylation mimic of K305） abolishes the activity by hindering tet- ramer formation. K422R, a patient-derived mutation of PKM2, favors a stable, inactive T-state tetramer because of strong intermolecular interactions. Our study reveals the mechanism for dynamic regulation of PKM2 by post- translational modifications and a patient-derived muta- tion and provides a structural basis for further investi- gation of other modifications and mutations of PKM2 yet to be discovered.展开更多
基金supported by the National Basic Research Program of China(973 program:2012CB910900)the National Natural Science Foundation of China(31200965 and31201106)+2 种基金the Guangdong Natural Science Foundation(S2012040006474)Start-up foundation of South China Botanical Garden the Chinese Academy of Sciences
文摘As sessile organisms, plants encounter various environmental stimuli including abiotic stresses during their lifecycle. To survive under adverse conditions, plants have evolved intricate mechanisms to perceive external signals and respond accordingly. Responses to various stresses largely depend on the plant capacity to modulate the transcriptome rapidly and specifically. A number of studies have shown that the molecular mechanisms driving the responses of plants to environmental stresses often depend on nucleosome histone post-translational modifications including histone acetylation, methylation, ubiquitination, and phosphorylation. The combined effects of these modifications play an essential role in the regulation of stress responsive gene expression. In this review, we highlight our current understanding of the epigenetic mechanisms of histone modifications and their roles in plant ahiotic stress response.
文摘TP53 is the most frequently mutated gene across all cancer types. Our understanding of its functions has evolved since its discovery four decades ago. Initially thought to be an oncogene, it was later realized to be a critical tumour suppressor. A significant amount of our knowledge about p53 functions have come from the use of antibodies against its various forms. The early anti-p53 antibodies contributed to the recognition of p53 accumulation as a common feature of cancer cells and to our understanding of p53 DNA-binding and transcription activities. They led to the concept that conformational changes can facilitate p53’s activity as a growth inhibitory protein. The ensuing p53 conformational-specific antibodies further underlined p53’s conformational flexibility, collectively forming the basis for current efforts to generate therapeutic molecules capable of altering the conformation of mutant p53. A subsequent barrage of antibodies against post-translational modifications on p53 has clarified p53’s roles further, especially with respect to the mechanistic details and context-dependence of its activity. More recently, the generation of p53 mutation-specific antibodies have highlighted the possibility to go beyond the general framework of our comprehension of mutant p53-and promises to provide insights into the specific properties of individual p53 mutants. This review summarizes our current knowledge of p53 functions derived through the major classes of anti-p53 antibodies, which could be a paradigm for understanding other molecular events in health and disease.
基金This work was supported by the National Key R&D Program of China(2016YFA0100400 and 2018YFC1004000)and the National Natural Science Foundation of China(31721003,31820103009,31701262,81630035).
文摘Mammalian fertilization begins with the fusion of two specialized gametes,followed by major epigenetic remodeling leading to the formation of a totipotent embryo.During the development of the pre-implantation embryo,precise reprogramming progress is a prerequisite for avoiding developmental defects or embryonic lethality,but the underlying molecular mechanisms remain elusive.For the past few years,unprecedented breakthroughs have been made in mapping the regulatory network of dynamic epigenomes during mammalian early embryo development,taking advantage of multiple advances and innovations in low-input genome-wide chromatin analysis technologies.The aim of this review is to highlight the most recent progress in understanding the mechanisms of epigenetic remodeling during early embryogenesis in mammals,including DNA methylation,histone modifications,chromatin accessibility and 3D chromatin organization.
基金This study was financially supported by the National Natural Science Foundation of China （Grant Nos. 31371602 and 91335107） and Specialized Research Fund for the Doctoral Program of Higher Education （20125103120008）.
文摘Although the molecular basis of flowering time control is well dissected in the long day （LD） plant Arabidopsis, it is still largely unknown in the short day （SD） plant rice. Rice flowering time （heading date） is an important agronomic trait for season adaption and grain yield, which is affected by both genetic and environmental factors. During the last decade, as the nature of florigen was identified, notable progress has been made on exploration how florigen gene ,expression is genetically controlled. In Arabidopsis expression of certain key flowering integrators such as FLOWERING LOCUS C （FLC） and FLOWERING LOCUS T （FT） are also epige- netically regulated by various chromatin modifications, however, very little is known in rice on this aspect until very recently. This review summarized the advances of both genetic networks and chromatin modifications in rice flowering time control, attempting to give a complete view of the genetic and epigenetic architecture in complex network of rice flowering pathways.
文摘Infiammasomes play essential roles in immune protection against microbial infections. However, excessive inflammation is implicated in various human diseases, including autoinflammatory syndromes, diabetes, multiple sclerosis, cardiovascular disorders and neurodegenerative diseases. Therefore, precise regulation of inflammasome activities is critical for adequate immune protection while limiting collateral tissue damage. In this review, we focus on the emerging roles of post-translational modifications （PTMs） that regulate activation of the NLRP3, NLRP1, NLRC4, AIM2 and IFI16 inflammasomes. We anticipate that these types of PTMs will be identified in other types of and less well-characterized inflammasomes. Because these highly diverse and versatile PTMs shape distinct inflammatory responses in response to infections and tissue damage, targeting the enzymes involved in these PTMs will undoubtedly offer opportunities for precise modulation of inflammasome activities under various pathophysiological conditions.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB27040203)the National Natural Science Foundation of China (No.31770155)
文摘Epigenetics refers to the study of heritable changes in gene function that do not involve changes in the DNA sequence. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors or be part of normal developmental program. In eukaryotes, DNA wraps on a histone octamer(two copies of H2A, H2B, H3 and H4) to form nucleosome, the fundamental unit of chromatin. The structure of chromatin is subjected to a dynamic regulation through multiple epigenetic mechanisms, including DNA methylation, histone posttranslational modifications(PTMs), chromatin remodeling and noncoding RNAs. As conserved regulatory mechanisms in gene expression, epigenetic mechanisms participate in almost all the important biological processes ranging from basal development to environmental response. Importantly, all of the major epigenetic mechanisms in mammalians also occur in plants. Plant studies have provided numerous important contributions to the epigenetic research. For example, gene imprinting, a mechanism of parental allele-specific gene expression, was firstly observed in maize; evidence of paramutation, an epigenetic phenomenon that one allele acts in a single locus to induce a heritable change in the other allele, was firstly reported in maize and tomato.Moreover, some unique epigenetic mechanisms have been evolved in plants. For example, the 24-nt siRNA-involved RNA-directed DNA methylation(RdDM) pathway is plant-specific because of the involvements of two plant-specific DNA-dependent RNA polymerases, Pol IV and Pol V. A thorough study of epigenetic mechanisms is of great significance to improve crop agronomic traits and environmental adaptability. In this review, we make a brief summary of important progress achieved in plant epigenetics field in China over the past several decades and give a brief outlook on future research prospects.We focus our review on DNA methylation and histone PTMs, the two most important aspects of epigenetic mechanisms.
文摘聚乳酸( PLA)具有独特的可生物降解性和生物相容性,是一种理想的 3D 打印材料。3D 打印 PLA 材料应用广泛,特别是在生物医用领域。然而,PLA 也存在着一些性能缺陷,在一定程度上限制了其在 3D 打印上的应用,因此需要对 PLA 进行改性。文章首先分析了 PLA 作为 3D 打印材料存在脆性大、耐热性差和易水解的性能缺陷;其次综述了 3D 打印 PLA 的改性方法,包括共聚改性、表面改性和共混改性;然后介绍了 3D 打印 PLA 材料的应用领域,包括生物医学领域和工业制造领域。最后文章介绍了具有优异耐热性和耐水解性的生物降解型立构聚乳酸,并对立构聚乳酸作为 3D 打印材料的前景进行了展望。
文摘Alcohol consumption causes cellular injury. Recent developments indicate that ethanol induces epigenetic alterations, particularly acetylation, methylation of histones, and hypo- and hypermethylation of DNA. This has opened up a new area of interest in ethanol research and is providing novel insight into actions of ethanol at the nucleosomal level in relation to gene expression and patho-physiological consequences. The epigenetic effects are mainly attributable to ethanol metabolic stress (Emess), generated by the oxidative and non-oxidative metabolism of ethanol, and dysregulation of methionine metabolism. Epigenetic changes are important in ethanol-induced hepatic steatosis, fibrosis, carcinoma and gastrointestinal injury. This editorial highlights these new advances and its future potential.
文摘Diabetes has become the epidemic of the 21 st century, and with over 90% patients with diabetes becoming at a risk of developing retinopathy, diabetic retinopathy has emerged as a major public health concern. In spite of cutting edge research in the field, how retina and its vasculature are damaged by the diabetic milieu remains ambiguous. The environmental factors, life style or disease process can also bring in modifications in the DNA, and these epigenetic modifications either silence or activate a gene without altering the DNA sequence. Diabetic environment up- or downregulates a number of genes in the retina, and emerging research has shown that it also facilitates epigenetic modifications. In the pathogenesis of diabetic retinopathy, the genes associated with important enzymes(e.g., mitochondrial superoxide dismutase, matrix metalloproteinase-9 and thioredoxin interacting protein) and transcriptional factors are epigenetically modified, the enzymes responsible for these epigenetic modifications are either activated or inhibited, and the levels of micro RNAs are altered. With epigenetic modifications taking an important place in diabetic retinopathy, it is now becoming critical to evaluate these modifications, and understand their impact on this slow progressing blinding disease.
基金Supported by Supported by a Research Grant of the University Medical Center Giessen and Marburg
文摘Inhibitors of protein deacetylases have recently been established as a novel therapeutic principle for several human diseases,including cancer.The original notion of the mechanism of action of these compounds focused on the epigenetic control of transcriptional processes, especially of tumor suppressor genes,by interfering with the acetylation status of nuclear histone proteins,hence the name histone deacetylase inhibitors was coined.Yet,this view could not explain the high specificity for tumor cells and recent evidence now suggests that non-histone proteins represent major targets for protein deacetylase inhibitors and that the post-translational modification of the acetylome is involved in various cellular processes of differentiation,survival and cell death induction.
文摘Pyruvate kinase isoform M2 （PKM2） converts phospho- enolpyruvate （PEP） to pyruvate and plays an important role in cancer metabolism. Here, we show that post- translational modifications and a patient-derived muta- tion regulate pyruvate kinase activity of PKM2 through modulating the conformation of the PKM2 tetramer. We determined crystal structures of human PKM2 mutants and proposed a ＂seesaw＂ model to illustrate confor- mational changes between an inactive T-state and an active R-state tetramers of PKM2. Biochemical and structural analyses demonstrate that PKM2^Y105E （phos- phorylation mimic of Y105） decreases pyruvate kinase activity by inhibiting FBP （fructose 1,6-bisphosphate）- induced R-state formation, and PKM2K^3305Q （acetylation mimic of K305） abolishes the activity by hindering tet- ramer formation. K422R, a patient-derived mutation of PKM2, favors a stable, inactive T-state tetramer because of strong intermolecular interactions. Our study reveals the mechanism for dynamic regulation of PKM2 by post- translational modifications and a patient-derived muta- tion and provides a structural basis for further investi- gation of other modifications and mutations of PKM2 yet to be discovered.
