DNA methylation represents a major type of DNA modifications that play key roles in diverse biological processes.With the recent development of highly selective and sensitive bioanalytical techniques,N^(6)-methyladeni...DNA methylation represents a major type of DNA modifications that play key roles in diverse biological processes.With the recent development of highly selective and sensitive bioanalytical techniques,N^(6)-methyladenine(6mA)has been characterized as an important internal DNA modification dynamically occurring in multiple eukaryotes including humans.Increasing evidence has indicated that 6mA may act as a novel epigenetic modification involved in regulation of development,stress response and diseases such as cancer and neurodegenerative disorders.We review herein the recent advances in the detection and functional studies of 6mA modification,with special emphasis on its biological consequences and human health relevance as well as its dynamic regulation by various types of methyltransferases,demethylases and 6mA-binding proteins.It can be envisaged that further chemical and biological studies of 6mA modification will lead to a better understanding about its potentially important roles in normal and pathological biological processes.展开更多
The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function a...The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function and signal transduction.Ophthalmic diseases are a kind of complex diseases,and their pathogenesis involves many factors such as genetic,environmental and individual differences.In addition,inflammation,oxidative stress and lipid metabolism,which abnormal DNA methylation is closely related to,are also considered to be major factors in eye diseases.The current understanding of DNA methylation in eye diseases is becoming more complex and comprehensive.In addition to the simple suppression of gene expression by hypermethylation,factors such as hypomethylation or demethylation,DNA methylation in non-promoter regions,interactions with other epigenetic modifications,and dynamic changes in DNA methylation must also be considered.Interestingly,although some genes are at abnormal methylation levels,their expression is not significantly changed,which indirectly reflects the complexity of gene regulation.This review aims to summarize and compare some relevant studies,and provide with new ideas and methods for the prevention and treatment of different eye diseases,such as glaucoma,retinoblastoma,and diabetic retinopathy.展开更多
Sleep deprivation(SD)is a widespread issue that disrupts the lives of millions of people.These effects ini-tiate as changes within neurons,specifically at the DNA and RNA level,leading to disruptions in neuronal plast...Sleep deprivation(SD)is a widespread issue that disrupts the lives of millions of people.These effects ini-tiate as changes within neurons,specifically at the DNA and RNA level,leading to disruptions in neuronal plasticity and the dysregulation of various cognitive functions,such as learning and memory.Nucleic acid epigenetic modifications that could regulate gene expression have been reported to play crucial roles in this process.However,there is a lack of comprehensive research on the correlation of SD with nucleic acid epigenetic modifications.In the current study,we aimed to systematically investigate the landscape of modifications in DNA as well as in small RNA molecules across multiple tissues,including the heart,liver,kidney,lung,hippocampus,and spleen,in response to chronic sleep deprivation(CSD).Using liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis,we characterized the dynamic changes in DNA and RNA modification profiles in different tissues of mice under CSD stress.Specifically,we ob-served a significant decrease in the level of 5-methylcytosine(5mC)and a significant increase in the level of 5-hydroxymethylcytosine(5hmC)in the kidney in CSD group.Regarding RNA modifications,we observed an overall increased trend for most of these significantly changed modifications across six tis-sues in CSD group.Our study sheds light on the significance of DNA and RNA modifications as crucial epigenetic markers in the context of CSD-induced stress.展开更多
Alcohol consumption is a critical risk factor contributing to a verity of human diseases. The incidence of alcohol use disorder increases across adolescence in recent years. Accumulating line of evidence suggests that...Alcohol consumption is a critical risk factor contributing to a verity of human diseases. The incidence of alcohol use disorder increases across adolescence in recent years. Accumulating line of evidence suggests that alcohol-induced changes of DNA cytosine methylation(5-methyl-2-deoxycytidine, 5 m C) in genomes play an important role in the development of diseases. However, systemic investigation of the effects of adolescent alcohol exposure on DNA and RNA modifications is still lacked. Especially, there hasn’t been any report to study the effects of alcohol exposure on RNA modifications. Similar to DNA modifications,RNA modifications recently have been identified to function as new regulators in modulating numbers of biological processes. In the current study, we systematically investigated the effects of alcohol exposure on both DNA and RNA modifications in peripheral blood of adolescent rats by liquid chromatographyelectrospray ionization-tandem mass spectrometry(LC-ESI-MS/MS) analysis. The developed LC-ESI-MS/MS method enabled the sensitive and accurate determination of 2 DNA modifications and 12 RNA modifications. As for the alcohol exposure experiments, the adolescent rats were intraperitoneally injected with ethanol with an interval of one day for a total 14 days. The quantification results by LC-ESI-MS/MS analysis showed that adolescent alcohol exposure could alter both DNA and RNA modifications in peripheral blood. Specifically, we observed an overall decreased trend of RNA modifications. The discovery of the significant alteration of the levels of DNA and RNA modifications under alcohol exposure indicates that alcohol consumption may increase the risk of the incidence and development of diseases through dysregulating DNA and RNA modifications.展开更多
Over 17 and 160 types of chemical modifications have been identified in DNA and RNA,respectively.The interest in understanding the various biological functions of DNA and RNA modifications has lead to the cutting-edge...Over 17 and 160 types of chemical modifications have been identified in DNA and RNA,respectively.The interest in understanding the various biological functions of DNA and RNA modifications has lead to the cutting-edged fields of epigenomics and epitranscriptomics.Developing chemical and biological tools to detect specific modifications in the genome or transcriptome has greatly facilitated their study.Here,we review the recent technological advances in this rapidly evolving field.We focus on high-throughput detection methods and biological findings for these modifications,and discuss questions to be addressed as well.We also summarize third-generation sequencing methods,which enable long-read and single-molecule sequencing of DNA and RNA modification.展开更多
In our previous studies, significant hypermethylation of the sirtuin 1（SIRT1） gene and demethylation of the b-amyloid precursor protein（APP） gene were found in patients with Alzheimer＇s disease（AD） compared wit...In our previous studies, significant hypermethylation of the sirtuin 1（SIRT1） gene and demethylation of the b-amyloid precursor protein（APP） gene were found in patients with Alzheimer＇s disease（AD） compared with the normal population. Moreover, the expression of SIRT1 was significantly decreased while that of APP was increased in AD patients. These results indicated a correlation of DNA methylation with gene expression levels in AD patients. To further investigate the epigenetic mechanism of gene modulation in AD, we used two epigenetic drugs, the DNA methylation inhibitor 5-aza-20-deoxycytidine（DAC） and the histone deacetylase inhibitor trichostatin A（TSA）, to treat human neuroblastoma SK-N-SH cells in the presence of amyloid b-peptide Ab25-35（Ab25-35）. We found that DAC and TSA had different effects on the expression trends of SIRT1 and APP in the cell model of amyloid toxicity. Although other genes, such as microtubule-associated protein s, presenilin 1, presenilin 2, and apolipoprotein E, were up-regulated after Ab25-35treatment, no significant differences were found after DAC and/or TSA treatment. These results support the evidence in AD patients and reveal a strong correlation of SIRT1/APP expression with DNA methylation and/or histone modification, which may help understand the pathogenesis of AD.展开更多
Genome editing is a valuable tool to target specific DNA sequences for mutagenesis in the genomes of microbes, plants, and animals. Although different genome editing technologies are available, the clustered regularly...Genome editing is a valuable tool to target specific DNA sequences for mutagenesis in the genomes of microbes, plants, and animals. Although different genome editing technologies are available, the clustered regularly interspaced short palindromic repeats/Cas9 （CRISPR/ Cas9） system, which utilizes engineered endonucleases to generate a double-stranded DNA break （DSB） in the target DNA region and subsequently stimulates site-specific mutagenesis through DNA repair machineries, is emerging as a powerful genome editing tool for elucidating mecha- nisms of protection from plant viruses, plant disease resistance, and gene functions in basic and applied research. In this review, we provide an overview of recent advances in the CRISPR system associated genome editing in plants by focusing on application of this technology in model plants, crop plants, fruit plants, woody plants and grasses and discuss how genome editing associated with the CRISPR system can provide insights into genome modifications and functional genomics in plants.展开更多
The global incidence of depression is progressively on the rise and tends to occur more in younger generations,however the pathogenesis of the disease is unclear.Meanwhile,epigenetics is a modification which produces ...The global incidence of depression is progressively on the rise and tends to occur more in younger generations,however the pathogenesis of the disease is unclear.Meanwhile,epigenetics is a modification which produces heritable alterations in the DNA sequence,which ultimately manifest in phenotypic differences.It has been suggested that the onset and development of depression can be tentatively explained by the combination of epigenetic and environmental factors.This paper reviews epigenetic changes in depression in the context of environmental factors,including DNA methylation modifications,histone modifications,and non-coding RNA regulation.An epigenetic-based therapeutic outlook was also proposed in this paper,which initially elucidates the epigenetic mechanisms underlying the pathogenesis of depressions and provides a theoretical basis for the treatment of depression.展开更多
The spatiotemporal expression of genes is sophisticatedly controlled through three main layers: transcriptional, translational and post-translational. Now increasing chemical modifications are discovered on genomic DN...The spatiotemporal expression of genes is sophisticatedly controlled through three main layers: transcriptional, translational and post-translational. Now increasing chemical modifications are discovered on genomic DNA, RNA and proteins. These modifications are recognized as additional layer of regulatory mechanisms in controlling gene expression that defines cell status. So far,more than 150 chemical modifications are identified in nucleic acids,and more than 400 discrete types of modifications are identified in proteins. How these modifications are interpreted are fundamental questions to our understanding of living organisms. The omics sciences of systems biology, including genomics, transcriptomics, proteomics, and metabolomics, have been in existence for decades. Due to the large numbers of modifications occurring in DNA, RNA and proteins with regulatory roles, we propose the modificaomics from the words of modification and omics. Modificaomics mainly refers to the comprehensive study of the modifications on DNA, RNA and proteins. In this review, we conceive modificaomics by introducing the discovered modifications in DNA, RNA and proteins as well as summarizing their biological functions. We hope the proposed modificaomics can provide a whole picture of modifications of these biopolymers and simulate the study of the functions of the modifications on DNA, RNA and proteins.展开更多
Here we tell a 20-year long story.It began with an easily overlooked DNA degradation(Dnd)phenomenon during electrophoresis and eventually led to the discovery of an unprecedented DNA sulfur modification governed by fi...Here we tell a 20-year long story.It began with an easily overlooked DNA degradation(Dnd)phenomenon during electrophoresis and eventually led to the discovery of an unprecedented DNA sulfur modification governed by five dnd genes.This unusual DNA modification,called phosphorothioation,is the first physiological modification identified on the DNA backbone,in which the nonbridging oxygen is replaced by sulfur in a sequence selective and stereo-specific manner.Homologous dnd gene clusters have been identified in diverse and distantly related bacteria and thus have drawn immediate attention of the entire microbial scientific community.Here,we summarize the progress in chemical,genetic,enzymatic,bioinformatical and analytical aspects of this novel postreplicative DNA modification.We also discuss perspectives on the physiological functions of the DNA phosphorothioate modification in bacteria and their implications.展开更多
Dynamic regulation and packaging of genetic information is achieved by the organization of DNA into chromatin. Nucleosomal core histones, which form the basic repeating unit of chromatin, are subject to various post-t...Dynamic regulation and packaging of genetic information is achieved by the organization of DNA into chromatin. Nucleosomal core histones, which form the basic repeating unit of chromatin, are subject to various post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitinylation. These modifications have effects on chromatin structure and, along with DNA methylation, regulate gene transcription.The goal of this study was to determine if patterns in modifications were related to different categories of genomic features, and, if so, if the patterns had predictive value. In this study, we used publically available data（ChIP-chip）for different types of histone modifications（methylation and acetylation） and for DNA methylation for Arabidopsis thaliana and then applied a machine learning based approach（a support vector machine） to demonstrate that patterns of these modifications are very different among different kinds of genomic feature categories（protein, RNA,pseudogene, and transposon elements）. These patterns can be used to distinguish the types of genomic features.DNA methylation and H3K4me3 methylation emerged as features with most discriminative power. From our analysis on Arabidopsis, we were able to predict 33 novel genomic features, whose existence was also supported by analysis of RNA-seq experiments. In summary, we present a novel approach which can be used to discriminate/detect different categories of genomic features based upon their patterns of chromatin modification and DNA methylation.展开更多
N^(6)-methyladenine(N^(6)-mA,m^(6)dA,or 6mA),a prevalent DNA modification in prokaryotes,has recently been identified in higher eukaryotes,including mammals.Although 6mA has been well-studied in prokaryotes,the functi...N^(6)-methyladenine(N^(6)-mA,m^(6)dA,or 6mA),a prevalent DNA modification in prokaryotes,has recently been identified in higher eukaryotes,including mammals.Although 6mA has been well-studied in prokaryotes,the function and regulatory mechanism of 6mA in eukaryotes are still poorly understood.Recent studies indicate that 6mA can serve as an epigenetic mark and play critical roles in various biological processes,from transposable-element suppression to environmental stress response.Here,we review the significant advances in methodology for 6mA detection and major progress in understanding the regulation and function of this non-canonical DNA methylation in eukaryotes,predominantly mammals.展开更多
Over 50 years of efforts, cellular reprogram- ruing opens a new door for disease modeling and regen- erative medicine. Although induction of pluripotency by transcription factors has become common, only a small portio...Over 50 years of efforts, cellular reprogram- ruing opens a new door for disease modeling and regen- erative medicine. Although induction of pluripotency by transcription factors has become common, only a small portion of basic mechanisms of epigenetic modifications during this process have been revealed. To clearly under- stand reprogramming and devise ways to promote full transition towards pluripotency, we must gain insight from comprehensive characterizations of cells at distinct repro- gramming stages, which involves gene expression profil- ing, chromatin state maps of key activating and repressive marks, and DNA modifications. Here, we review recent advances in epigenetic reprogramming to pluripotency with a focus on the principal molecular regulators and attach importance to the combination of high-throughput sequencing and systematic biology approaches in uncov- ering underlying molecular mechanisms of this unique platform in future researches.展开更多
Lingguizhugan Decoction(LGZG)has been investigated in basic studies,with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease(NAFLD).This translational approach aimed to explore the effect a...Lingguizhugan Decoction(LGZG)has been investigated in basic studies,with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease(NAFLD).This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting.A randomized,double-blinded,placebo-controlled trial was performed.A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG(two groups:standard dose and low dose)or placebo for 12 weeks on the basis of lifestyle modifications.The primary efficacy variable was homeostasis model assessment of insulin resistance(HOMA-IR).Analyses were performed in two populations in accordance with body mass index(BMI;overweight/obese,BMI 24 kg/m^(2);lean,BMI<24 kg/m^(2)).For overweight/obese participants,low-dose LGZG significantly decreased their HOMA-IR level compared with placebo(0.19(1.47)versus 0.08(1.99),P=0.038).For lean subjects,neither dose of LGZG showed a superior effect compared with placebo.Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A(PPP1R3A)and autophagy related 3(ATG3)significantly increased after LGZG intervention in overweight/obese population.Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD.The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3.Lean subjects may not be a targeted population for LGZG.展开更多
Post-transcriptional modifications,including histone modifications and DNA methylation,alter the chromatin landscape to regulate gene expression,thus control various cellular processes in plants.EARLY FLOWERING IN SHO...Post-transcriptional modifications,including histone modifications and DNA methylation,alter the chromatin landscape to regulate gene expression,thus control various cellular processes in plants.EARLY FLOWERING IN SHORT DAYS(EFS)is the major contributor for H3K36 methylation in Arabidopsis and is important for plant development.Here,we find that EFS is expressed in different stages of embryo morphogenesis,and the efs mutant produces larger embryo that results in enlarged seeds.Further analysis reveals that an imprinted gene MOP9.5 is hypomethylated at the promoter region and its expression is derepressed in efs mutant.MOP9.5 promoter is marked by various epigenetic modifications,and we find that following the increase of H3K36me3,H3K27me3 and H3K9me2 levels are reduced in efs mutant.This data indicates an antagonistic regulation between H3K36me3 and DNA methylation,and/or H3K27me3 at MOP9.5.Our results further show that both maternal and paternal EFS alleles are responsible for the seed size regulation,which unraveled a novel function of EFS in plant development.展开更多
基金supported by the National Natural Science Foun-dation of China(Nos.21807030,21907028)the Science and Tech-nology Innovation Program of Hunan Province(No.2019RS2020),Natural Science Foundation of Hunan Province(No.2020JJ5046)the Fundamental Research Funds for the Central Universities(Nos.531118010061,531118010259).
文摘DNA methylation represents a major type of DNA modifications that play key roles in diverse biological processes.With the recent development of highly selective and sensitive bioanalytical techniques,N^(6)-methyladenine(6mA)has been characterized as an important internal DNA modification dynamically occurring in multiple eukaryotes including humans.Increasing evidence has indicated that 6mA may act as a novel epigenetic modification involved in regulation of development,stress response and diseases such as cancer and neurodegenerative disorders.We review herein the recent advances in the detection and functional studies of 6mA modification,with special emphasis on its biological consequences and human health relevance as well as its dynamic regulation by various types of methyltransferases,demethylases and 6mA-binding proteins.It can be envisaged that further chemical and biological studies of 6mA modification will lead to a better understanding about its potentially important roles in normal and pathological biological processes.
文摘The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function and signal transduction.Ophthalmic diseases are a kind of complex diseases,and their pathogenesis involves many factors such as genetic,environmental and individual differences.In addition,inflammation,oxidative stress and lipid metabolism,which abnormal DNA methylation is closely related to,are also considered to be major factors in eye diseases.The current understanding of DNA methylation in eye diseases is becoming more complex and comprehensive.In addition to the simple suppression of gene expression by hypermethylation,factors such as hypomethylation or demethylation,DNA methylation in non-promoter regions,interactions with other epigenetic modifications,and dynamic changes in DNA methylation must also be considered.Interestingly,although some genes are at abnormal methylation levels,their expression is not significantly changed,which indirectly reflects the complexity of gene regulation.This review aims to summarize and compare some relevant studies,and provide with new ideas and methods for the prevention and treatment of different eye diseases,such as glaucoma,retinoblastoma,and diabetic retinopathy.
基金supported by the National Key R&D Program of China(Nos.2022YFC3400700,2022YFA0806600)the National Natural Science Foundation of China(Nos.22277093,22074110,21721005)+2 种基金the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University(No.JCRCGW-2022-008)the Wuhan Knowledge Innovation Project(No.2022020801010111)the Natural Science Foundation of Hubei Province(No.2022CFB569).
文摘Sleep deprivation(SD)is a widespread issue that disrupts the lives of millions of people.These effects ini-tiate as changes within neurons,specifically at the DNA and RNA level,leading to disruptions in neuronal plasticity and the dysregulation of various cognitive functions,such as learning and memory.Nucleic acid epigenetic modifications that could regulate gene expression have been reported to play crucial roles in this process.However,there is a lack of comprehensive research on the correlation of SD with nucleic acid epigenetic modifications.In the current study,we aimed to systematically investigate the landscape of modifications in DNA as well as in small RNA molecules across multiple tissues,including the heart,liver,kidney,lung,hippocampus,and spleen,in response to chronic sleep deprivation(CSD).Using liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis,we characterized the dynamic changes in DNA and RNA modification profiles in different tissues of mice under CSD stress.Specifically,we ob-served a significant decrease in the level of 5-methylcytosine(5mC)and a significant increase in the level of 5-hydroxymethylcytosine(5hmC)in the kidney in CSD group.Regarding RNA modifications,we observed an overall increased trend for most of these significantly changed modifications across six tis-sues in CSD group.Our study sheds light on the significance of DNA and RNA modifications as crucial epigenetic markers in the context of CSD-induced stress.
基金supported by the National Natural Science Foundation of China (Nos. 22074110, 21635006, 21721005, 31771193)the Fundamental Research Funds for the Central Universities (No.2042021kf0212)。
文摘Alcohol consumption is a critical risk factor contributing to a verity of human diseases. The incidence of alcohol use disorder increases across adolescence in recent years. Accumulating line of evidence suggests that alcohol-induced changes of DNA cytosine methylation(5-methyl-2-deoxycytidine, 5 m C) in genomes play an important role in the development of diseases. However, systemic investigation of the effects of adolescent alcohol exposure on DNA and RNA modifications is still lacked. Especially, there hasn’t been any report to study the effects of alcohol exposure on RNA modifications. Similar to DNA modifications,RNA modifications recently have been identified to function as new regulators in modulating numbers of biological processes. In the current study, we systematically investigated the effects of alcohol exposure on both DNA and RNA modifications in peripheral blood of adolescent rats by liquid chromatographyelectrospray ionization-tandem mass spectrometry(LC-ESI-MS/MS) analysis. The developed LC-ESI-MS/MS method enabled the sensitive and accurate determination of 2 DNA modifications and 12 RNA modifications. As for the alcohol exposure experiments, the adolescent rats were intraperitoneally injected with ethanol with an interval of one day for a total 14 days. The quantification results by LC-ESI-MS/MS analysis showed that adolescent alcohol exposure could alter both DNA and RNA modifications in peripheral blood. Specifically, we observed an overall decreased trend of RNA modifications. The discovery of the significant alteration of the levels of DNA and RNA modifications under alcohol exposure indicates that alcohol consumption may increase the risk of the incidence and development of diseases through dysregulating DNA and RNA modifications.
基金This work was supported by the National Natural Science Foundation of China(Grant No.31861143026 to C.Y.)the Ministry of Science and Technology of China(Grant Nos.2019YFA0110902 and 2019YFA08002501 to C.Y.)the Ludwig Institute for Cancer Research(C-X.S.),Cancer Research UK(C63763/A26394 and C63763/A27122 to C-X.S.)NIHR Oxford Biomedical Research Centre(to C-X.S.)and Emerson Collective(to C-X.S.).L-Y.Z.is supported by China Scholarship Council.The views expressed are those of the authors and not necessarily those of the NHS,the NIHR or the Department of Health.We apologize for not being able to cite all the publications related to this topic due to space constraints of the journal.
文摘Over 17 and 160 types of chemical modifications have been identified in DNA and RNA,respectively.The interest in understanding the various biological functions of DNA and RNA modifications has lead to the cutting-edged fields of epigenomics and epitranscriptomics.Developing chemical and biological tools to detect specific modifications in the genome or transcriptome has greatly facilitated their study.Here,we review the recent technological advances in this rapidly evolving field.We focus on high-throughput detection methods and biological findings for these modifications,and discuss questions to be addressed as well.We also summarize third-generation sequencing methods,which enable long-read and single-molecule sequencing of DNA and RNA modification.
基金supported by the National Basic Research Development Program of China (2006cb500700)the National Natural Science Foundation of China (30470904 and 31401627)+3 种基金Guangdong Provincial Natural Science Foundation of China (2010B031600070 and 2015A030313066)Science and Technology Social Development Project of Guangdong Province (2008B030301320 and 2012B031800053)a Guangdong Provincial Science and Technology Project (2013B051000009)a Guangzhou Science and Technology Plan Application Basic Research Project (2012J410076)
文摘In our previous studies, significant hypermethylation of the sirtuin 1（SIRT1） gene and demethylation of the b-amyloid precursor protein（APP） gene were found in patients with Alzheimer＇s disease（AD） compared with the normal population. Moreover, the expression of SIRT1 was significantly decreased while that of APP was increased in AD patients. These results indicated a correlation of DNA methylation with gene expression levels in AD patients. To further investigate the epigenetic mechanism of gene modulation in AD, we used two epigenetic drugs, the DNA methylation inhibitor 5-aza-20-deoxycytidine（DAC） and the histone deacetylase inhibitor trichostatin A（TSA）, to treat human neuroblastoma SK-N-SH cells in the presence of amyloid b-peptide Ab25-35（Ab25-35）. We found that DAC and TSA had different effects on the expression trends of SIRT1 and APP in the cell model of amyloid toxicity. Although other genes, such as microtubule-associated protein s, presenilin 1, presenilin 2, and apolipoprotein E, were up-regulated after Ab25-35treatment, no significant differences were found after DAC and/or TSA treatment. These results support the evidence in AD patients and reveal a strong correlation of SIRT1/APP expression with DNA methylation and/or histone modification, which may help understand the pathogenesis of AD.
文摘Genome editing is a valuable tool to target specific DNA sequences for mutagenesis in the genomes of microbes, plants, and animals. Although different genome editing technologies are available, the clustered regularly interspaced short palindromic repeats/Cas9 （CRISPR/ Cas9） system, which utilizes engineered endonucleases to generate a double-stranded DNA break （DSB） in the target DNA region and subsequently stimulates site-specific mutagenesis through DNA repair machineries, is emerging as a powerful genome editing tool for elucidating mecha- nisms of protection from plant viruses, plant disease resistance, and gene functions in basic and applied research. In this review, we provide an overview of recent advances in the CRISPR system associated genome editing in plants by focusing on application of this technology in model plants, crop plants, fruit plants, woody plants and grasses and discuss how genome editing associated with the CRISPR system can provide insights into genome modifications and functional genomics in plants.
文摘The global incidence of depression is progressively on the rise and tends to occur more in younger generations,however the pathogenesis of the disease is unclear.Meanwhile,epigenetics is a modification which produces heritable alterations in the DNA sequence,which ultimately manifest in phenotypic differences.It has been suggested that the onset and development of depression can be tentatively explained by the combination of epigenetic and environmental factors.This paper reviews epigenetic changes in depression in the context of environmental factors,including DNA methylation modifications,histone modifications,and non-coding RNA regulation.An epigenetic-based therapeutic outlook was also proposed in this paper,which initially elucidates the epigenetic mechanisms underlying the pathogenesis of depressions and provides a theoretical basis for the treatment of depression.
基金supported by the National Key R&D Program of China(2017YFC0906800)the National Natural Science Foundation of China(21522507,21672166,21635006,21721005)
文摘The spatiotemporal expression of genes is sophisticatedly controlled through three main layers: transcriptional, translational and post-translational. Now increasing chemical modifications are discovered on genomic DNA, RNA and proteins. These modifications are recognized as additional layer of regulatory mechanisms in controlling gene expression that defines cell status. So far,more than 150 chemical modifications are identified in nucleic acids,and more than 400 discrete types of modifications are identified in proteins. How these modifications are interpreted are fundamental questions to our understanding of living organisms. The omics sciences of systems biology, including genomics, transcriptomics, proteomics, and metabolomics, have been in existence for decades. Due to the large numbers of modifications occurring in DNA, RNA and proteins with regulatory roles, we propose the modificaomics from the words of modification and omics. Modificaomics mainly refers to the comprehensive study of the modifications on DNA, RNA and proteins. In this review, we conceive modificaomics by introducing the discovered modifications in DNA, RNA and proteins as well as summarizing their biological functions. We hope the proposed modificaomics can provide a whole picture of modifications of these biopolymers and simulate the study of the functions of the modifications on DNA, RNA and proteins.
文摘Here we tell a 20-year long story.It began with an easily overlooked DNA degradation(Dnd)phenomenon during electrophoresis and eventually led to the discovery of an unprecedented DNA sulfur modification governed by five dnd genes.This unusual DNA modification,called phosphorothioation,is the first physiological modification identified on the DNA backbone,in which the nonbridging oxygen is replaced by sulfur in a sequence selective and stereo-specific manner.Homologous dnd gene clusters have been identified in diverse and distantly related bacteria and thus have drawn immediate attention of the entire microbial scientific community.Here,we summarize the progress in chemical,genetic,enzymatic,bioinformatical and analytical aspects of this novel postreplicative DNA modification.We also discuss perspectives on the physiological functions of the DNA phosphorothioate modification in bacteria and their implications.
基金supported by the National Science Foundation of USA(No.IIS 0916250)The University of Georgia Franklin College of Arts&Sciences research fund
文摘Dynamic regulation and packaging of genetic information is achieved by the organization of DNA into chromatin. Nucleosomal core histones, which form the basic repeating unit of chromatin, are subject to various post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitinylation. These modifications have effects on chromatin structure and, along with DNA methylation, regulate gene transcription.The goal of this study was to determine if patterns in modifications were related to different categories of genomic features, and, if so, if the patterns had predictive value. In this study, we used publically available data（ChIP-chip）for different types of histone modifications（methylation and acetylation） and for DNA methylation for Arabidopsis thaliana and then applied a machine learning based approach（a support vector machine） to demonstrate that patterns of these modifications are very different among different kinds of genomic feature categories（protein, RNA,pseudogene, and transposon elements）. These patterns can be used to distinguish the types of genomic features.DNA methylation and H3K4me3 methylation emerged as features with most discriminative power. From our analysis on Arabidopsis, we were able to predict 33 novel genomic features, whose existence was also supported by analysis of RNA-seq experiments. In summary, we present a novel approach which can be used to discriminate/detect different categories of genomic features based upon their patterns of chromatin modification and DNA methylation.
基金This work is supported by grants from CPRIT(RR180072)Rivkin Center Scientific Scholar Award.
文摘N^(6)-methyladenine(N^(6)-mA,m^(6)dA,or 6mA),a prevalent DNA modification in prokaryotes,has recently been identified in higher eukaryotes,including mammals.Although 6mA has been well-studied in prokaryotes,the function and regulatory mechanism of 6mA in eukaryotes are still poorly understood.Recent studies indicate that 6mA can serve as an epigenetic mark and play critical roles in various biological processes,from transposable-element suppression to environmental stress response.Here,we review the significant advances in methodology for 6mA detection and major progress in understanding the regulation and function of this non-canonical DNA methylation in eukaryotes,predominantly mammals.
基金supported by the National Natural Science Foundation of China(31325019,91319306 and31401247)Ministry of Science and Technology of China(2015CB964800 and 2014CB964601)
文摘Over 50 years of efforts, cellular reprogram- ruing opens a new door for disease modeling and regen- erative medicine. Although induction of pluripotency by transcription factors has become common, only a small portion of basic mechanisms of epigenetic modifications during this process have been revealed. To clearly under- stand reprogramming and devise ways to promote full transition towards pluripotency, we must gain insight from comprehensive characterizations of cells at distinct repro- gramming stages, which involves gene expression profil- ing, chromatin state maps of key activating and repressive marks, and DNA modifications. Here, we review recent advances in epigenetic reprogramming to pluripotency with a focus on the principal molecular regulators and attach importance to the combination of high-throughput sequencing and systematic biology approaches in uncov- ering underlying molecular mechanisms of this unique platform in future researches.
基金This study is supported by the National Natural Science Foundation of China(No.816220108030)the Evidence-based Capacity Building Project for Basic Traditional Chinese Medicine-Specialized Diseases(No.2019XZZX-XH012)Shanghai Three-year Action Planfor Accelerating the Development of Traditional Chinese Medicine(ZY(2018-2020)-CCCX-2002-01).
文摘Lingguizhugan Decoction(LGZG)has been investigated in basic studies,with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease(NAFLD).This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting.A randomized,double-blinded,placebo-controlled trial was performed.A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG(two groups:standard dose and low dose)or placebo for 12 weeks on the basis of lifestyle modifications.The primary efficacy variable was homeostasis model assessment of insulin resistance(HOMA-IR).Analyses were performed in two populations in accordance with body mass index(BMI;overweight/obese,BMI 24 kg/m^(2);lean,BMI<24 kg/m^(2)).For overweight/obese participants,low-dose LGZG significantly decreased their HOMA-IR level compared with placebo(0.19(1.47)versus 0.08(1.99),P=0.038).For lean subjects,neither dose of LGZG showed a superior effect compared with placebo.Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A(PPP1R3A)and autophagy related 3(ATG3)significantly increased after LGZG intervention in overweight/obese population.Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD.The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3.Lean subjects may not be a targeted population for LGZG.
基金supported by National Key R&D Program (2016YFA0500800)the National Natural Science Foundation of China (31571322)+2 种基金Tsinghua-Peking Joint Center for Life Sciences1000 Young Talent Program of ChinaS.Shafiq and Wei Xu are supported by the postdoctoral fellowships from Tsinghua-Peking Joint Center for Life Sciences
文摘Post-transcriptional modifications,including histone modifications and DNA methylation,alter the chromatin landscape to regulate gene expression,thus control various cellular processes in plants.EARLY FLOWERING IN SHORT DAYS(EFS)is the major contributor for H3K36 methylation in Arabidopsis and is important for plant development.Here,we find that EFS is expressed in different stages of embryo morphogenesis,and the efs mutant produces larger embryo that results in enlarged seeds.Further analysis reveals that an imprinted gene MOP9.5 is hypomethylated at the promoter region and its expression is derepressed in efs mutant.MOP9.5 promoter is marked by various epigenetic modifications,and we find that following the increase of H3K36me3,H3K27me3 and H3K9me2 levels are reduced in efs mutant.This data indicates an antagonistic regulation between H3K36me3 and DNA methylation,and/or H3K27me3 at MOP9.5.Our results further show that both maternal and paternal EFS alleles are responsible for the seed size regulation,which unraveled a novel function of EFS in plant development.
