DNA methylation plays a crucial role in regulating plant development and tissue differentiation. In this study, we compared the methylation levels in leaf, root, and stem in Chamaedorea elegans by using the technique ...DNA methylation plays a crucial role in regulating plant development and tissue differentiation. In this study, we compared the methylation levels in leaf, root, and stem in Chamaedorea elegans by using the technique of methylation-sensitive amplified fragment length polymorphism AFLP. Over 19% （42/220） bases were uniformly methy- lated in these tissues. The percentages of polymorphism resulting from varied methylation in mature leaf （L1）, young leaf （L2）, baby leaf （L3）, stem （S）, young root （R1） and lignified root （R2） were 29.5%, 29.0%, 27.1%, 30.7%, 63.0% and 28.3%, respectively. The numbers of poly- morphic loci detected in the leaves of three developmental stages were similar, ranging from 20 to 30. In contrast, roots at the two developmental stages differed greatly, with 145 polymorphic loci detected in R1 and 27 in R2. Our results suggest that the methylation level in leaves slightly increases with aging, while that in roots decreases dramatically with aging.展开更多
Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring.However,the precise epigenetic mechanisms governing these intergenerational effects,pa...Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring.However,the precise epigenetic mechanisms governing these intergenerational effects,particularly during the early stages of offspring development,remain poorly understood.In this study,female C57BL/6J mice were randomly assigned to either a high-fat diet or normal chow diet throughout gestation and lactation.Methylated DNA immunoprecipitation(MeDIP)coupled with microarray analysis was employed to identify differentially methylated genes in the livers of offspring at weaning age.We found that maternal high-fat diet feeding predisposes offspring to obesity and impaired glucose metabolism as early as the weaning period.DNA methylation profile analysis unveiled a significant enrichment of differentially methylated genes within the natural killer(NK)cell-mediated cytotoxicity pathway.MeDIP-PCR validated reduced methylation levels of specific genes within this pathway,including tumour necrosis factorα(TNF-α),phosphoinositide 3-kinase(PI3K),and SHC adaptor protein 1(SHC1).Consistently,the expressions of TNF-α,PI3K,and SHC1 were significantly upregulated,accompanied by elevated serum TNF-αand interleukin-6(IL-6)levels in offspring from dams fed with high-fat diet.Moreover,we assessed the expressions of genes associated with NK cell activities,uncovering a notable rise in hepatic granzyme B levels and a trend towards increased CD107a expression in offspring from dams fed a high-fat diet.In addition,methylation levels of TNF-α,PI3K,and SHC1 promoters were inversely correlated with glucose response during glucose tolerance testing.In conclusion,our findings underscore the critical role of the NK cell-mediated cytotoxicity signaling pathway in mediating DNA methylation patterns,thereby contributing to the programming effects of maternal high-fat diet consumption on offspring glucose metabolism as early as the weaning period.展开更多
Methylation in the bases of DNA is known to induce B-Z conformation change. In this work, molecular mechanics and normal mode analysis are used to probe how certain methylation affects the internal interactions and th...Methylation in the bases of DNA is known to induce B-Z conformation change. In this work, molecular mechanics and normal mode analysis are used to probe how certain methylation affects the internal interactions and thermodynamic motions in the DNA double helixes in both B and Z conformations, and its implication to B-Z conformation change. By molecular modeling with Insight II, two cases involving cytosine C5 and guanine C8 methylation on both B and Z-form DNA duplex d(CGCGCG)2 are studied in comparison with the corresponding unmethylated duplexes. The internal interaction energies computed based on a molecular mechanics force field and the entropies due to internal motions computed according to a normal mode analysis are in fare agreement with respective observed thermodynamic quantities. The analysis on the computed individual energy terms suggests that the observed B-Z conformation change induced by methylation is primarily driven by enthalpic factors. A combination of changes in Van der Waals interaction, electrostatic interaction and hydrogen bonding likely contributes to the change of enthalpy that favors Z-conformation in the methylated states.展开更多
Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease(KBD).We also analyzed the i...Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease(KBD).We also analyzed the interaction between the CpGs methylations and CpG-SNPs.Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects.Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry(MALDI-TOF-MS).The CpGs methylation levels were compared between samples from KBD patients and healthy subjects.The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes.Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls(P<0.05).The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls(P<0.05).The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls.The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype(P<0.05).Conclusion The methylation level of DIO2 increases in KBD patients.Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.展开更多
The Betula genus contains pentacyclic triterpenoid betulin known for its environmental adaptation and medicinal properties.However,the mechanisms underlying betulin biosynthesis responding to climate change remain unc...The Betula genus contains pentacyclic triterpenoid betulin known for its environmental adaptation and medicinal properties.However,the mechanisms underlying betulin biosynthesis responding to climate change remain unclear.In this study,the role of epigenetic modification(DNA methylation) in betulin biosynthesis was examined and how climatic factors influence it.Whole-genome bisulfite sequencing was performed for greenhouse-grown Chinese white birch(Betula platyphylla Sukaczev) treated with DNA methylation inhibitor zebularine(ZEB) and a natural birch population in Northeast China.ZEB treatment significantly affected the CHH methylation level of transposable elements and betulin content in a hormesis dose-dependent manner.The methylation and expression of bHLH9,a key transcriptional factor controlling betulin biosynthesis,were also consistently affected by ZEB treatment as a hormetic dose-response.In the natural population,there was a positive correlation between promoter methylation of bHLH9 and summer precipitation,while winter temperature was negatively correlated.Thus climate-dependent methylation of bHLH9 regulates the expression of downstream genes involved in betulin biosynthesis.This study highlights the role of environmental signals to induce epigenetic changes that result in betulin production,possibly helping to develop resilient plants to combat ongoing climate change and enhance secondary metabolite production.展开更多
Nicotinamide treatment of plants and plant cell cultures has been shown to promote defense and decrease levels of DNA methylation.In the present study,we used RNA-seq technology to study overall changes in gene expres...Nicotinamide treatment of plants and plant cell cultures has been shown to promote defense and decrease levels of DNA methylation.In the present study,we used RNA-seq technology to study overall changes in gene expression induced in roots of 3-month-old spruce(Picea abies)seedlings grown from nicotinamide-treated seeds to examine the molecular mechanisms underlying the defense promotion.Approximately 350 genes were identified as differentially expressed in roots after the seed treatment.Stress response genes,including transcription factors MYB77 and LHY and two chitinase enzymes,were generally upregulated,whereas genes thought to be involved in epigenetic regulation such as DDM1,known to promote DNA methylation,were present at high frequency among the downregulated genes.Across all samples,the expression of downregulated epigenetic-related genes was highly correlated with the nicotinamide treatment,indicating a common regulation.Our results support an earlier hypothesis regarding a potential role of nicotinamide as a defense-signal mediator.展开更多
基金supported by the Natural Science Foundation of China (30800879)
文摘DNA methylation plays a crucial role in regulating plant development and tissue differentiation. In this study, we compared the methylation levels in leaf, root, and stem in Chamaedorea elegans by using the technique of methylation-sensitive amplified fragment length polymorphism AFLP. Over 19% （42/220） bases were uniformly methy- lated in these tissues. The percentages of polymorphism resulting from varied methylation in mature leaf （L1）, young leaf （L2）, baby leaf （L3）, stem （S）, young root （R1） and lignified root （R2） were 29.5%, 29.0%, 27.1%, 30.7%, 63.0% and 28.3%, respectively. The numbers of poly- morphic loci detected in the leaves of three developmental stages were similar, ranging from 20 to 30. In contrast, roots at the two developmental stages differed greatly, with 145 polymorphic loci detected in R1 and 27 in R2. Our results suggest that the methylation level in leaves slightly increases with aging, while that in roots decreases dramatically with aging.
基金sponsored by National Natural Science Foundation of China(81800703)Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20231088)+8 种基金Beijing Nova Program(Z201100006820117 and 20220484181)Beijing Municipal Natural Science Foundation(7184252)the Fundamental Research Funds for the Central Universitiesthe Fundamental Research Funds for the Central Universities(BMU2021MX013)Peking University Clinical Scientist Training Program(BMU2023PYJH022)Peking University Medicine Seed Fund for Interdisciplinary ResearchChina Endocrine and Metabolism Young Scientific Talent Research Project(2022-N-02-01)China Diabetes Young Scientific Talent Research ProjectBethune-Merck Diabetes Research Fund of Bethune Charitable Foundation。
文摘Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring.However,the precise epigenetic mechanisms governing these intergenerational effects,particularly during the early stages of offspring development,remain poorly understood.In this study,female C57BL/6J mice were randomly assigned to either a high-fat diet or normal chow diet throughout gestation and lactation.Methylated DNA immunoprecipitation(MeDIP)coupled with microarray analysis was employed to identify differentially methylated genes in the livers of offspring at weaning age.We found that maternal high-fat diet feeding predisposes offspring to obesity and impaired glucose metabolism as early as the weaning period.DNA methylation profile analysis unveiled a significant enrichment of differentially methylated genes within the natural killer(NK)cell-mediated cytotoxicity pathway.MeDIP-PCR validated reduced methylation levels of specific genes within this pathway,including tumour necrosis factorα(TNF-α),phosphoinositide 3-kinase(PI3K),and SHC adaptor protein 1(SHC1).Consistently,the expressions of TNF-α,PI3K,and SHC1 were significantly upregulated,accompanied by elevated serum TNF-αand interleukin-6(IL-6)levels in offspring from dams fed with high-fat diet.Moreover,we assessed the expressions of genes associated with NK cell activities,uncovering a notable rise in hepatic granzyme B levels and a trend towards increased CD107a expression in offspring from dams fed a high-fat diet.In addition,methylation levels of TNF-α,PI3K,and SHC1 promoters were inversely correlated with glucose response during glucose tolerance testing.In conclusion,our findings underscore the critical role of the NK cell-mediated cytotoxicity signaling pathway in mediating DNA methylation patterns,thereby contributing to the programming effects of maternal high-fat diet consumption on offspring glucose metabolism as early as the weaning period.
基金the International Joint Research Project of Chongqing University and National University of Singapore (ARF-151-000-014-112) and the Basic and Applied Research Foundation of Chongqing University.
文摘Methylation in the bases of DNA is known to induce B-Z conformation change. In this work, molecular mechanics and normal mode analysis are used to probe how certain methylation affects the internal interactions and thermodynamic motions in the DNA double helixes in both B and Z conformations, and its implication to B-Z conformation change. By molecular modeling with Insight II, two cases involving cytosine C5 and guanine C8 methylation on both B and Z-form DNA duplex d(CGCGCG)2 are studied in comparison with the corresponding unmethylated duplexes. The internal interaction energies computed based on a molecular mechanics force field and the entropies due to internal motions computed according to a normal mode analysis are in fare agreement with respective observed thermodynamic quantities. The analysis on the computed individual energy terms suggests that the observed B-Z conformation change induced by methylation is primarily driven by enthalpic factors. A combination of changes in Van der Waals interaction, electrostatic interaction and hydrogen bonding likely contributes to the change of enthalpy that favors Z-conformation in the methylated states.
基金supported by the National Natural Science Foundation of China(82073494)Key Re-search and Development Program of Shaanxi Prov-ince(2020SF-076)+1 种基金Special R&D Program Proj-ect of Chinese Academy of Se-enriched Industry(2020FXZX0501)the Subject Innovation Team of Shaanxi University of Chinese Medicine(132041933).
文摘Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease(KBD).We also analyzed the interaction between the CpGs methylations and CpG-SNPs.Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects.Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry(MALDI-TOF-MS).The CpGs methylation levels were compared between samples from KBD patients and healthy subjects.The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes.Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls(P<0.05).The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls(P<0.05).The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls.The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype(P<0.05).Conclusion The methylation level of DIO2 increases in KBD patients.Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.
基金the National Non-profi t Institute Research Grant of the Chinese Academy of Forestry(CAFYBB2019ZY003)the National Natural Science Foundation of China(31871220 and 31801444)+2 种基金the Innovation Project of State Key Laboratory of Tree Genetics andBreeding(Northeast Forestry University)(2013A06)the Fundamental Research Funds for the Central Universities(2572017DA06 and 2572020DP01)Heilongjiang Provincial Natural Science Foundation of China(LH2021C005).
文摘The Betula genus contains pentacyclic triterpenoid betulin known for its environmental adaptation and medicinal properties.However,the mechanisms underlying betulin biosynthesis responding to climate change remain unclear.In this study,the role of epigenetic modification(DNA methylation) in betulin biosynthesis was examined and how climatic factors influence it.Whole-genome bisulfite sequencing was performed for greenhouse-grown Chinese white birch(Betula platyphylla Sukaczev) treated with DNA methylation inhibitor zebularine(ZEB) and a natural birch population in Northeast China.ZEB treatment significantly affected the CHH methylation level of transposable elements and betulin content in a hormesis dose-dependent manner.The methylation and expression of bHLH9,a key transcriptional factor controlling betulin biosynthesis,were also consistently affected by ZEB treatment as a hormetic dose-response.In the natural population,there was a positive correlation between promoter methylation of bHLH9 and summer precipitation,while winter temperature was negatively correlated.Thus climate-dependent methylation of bHLH9 regulates the expression of downstream genes involved in betulin biosynthesis.This study highlights the role of environmental signals to induce epigenetic changes that result in betulin production,possibly helping to develop resilient plants to combat ongoing climate change and enhance secondary metabolite production.
基金supported by AForsk(https://aforsk.com)[15-416]Stiftelsen Tornspiran(http://stiftelsentornspiran.se)+2 种基金Anna och Nils Hakanssons Stiftelse(http://www.annaochnilshakanssonsstiftelse.se)Helge Ax:son Johnsons stiftelse(http://haxsonj.se/www/)[770721-0204]Magnus Bergvalls Stiftelse(http://www.magnbergvallsstiftelse.nu)[2014-00501]。
文摘Nicotinamide treatment of plants and plant cell cultures has been shown to promote defense and decrease levels of DNA methylation.In the present study,we used RNA-seq technology to study overall changes in gene expression induced in roots of 3-month-old spruce(Picea abies)seedlings grown from nicotinamide-treated seeds to examine the molecular mechanisms underlying the defense promotion.Approximately 350 genes were identified as differentially expressed in roots after the seed treatment.Stress response genes,including transcription factors MYB77 and LHY and two chitinase enzymes,were generally upregulated,whereas genes thought to be involved in epigenetic regulation such as DDM1,known to promote DNA methylation,were present at high frequency among the downregulated genes.Across all samples,the expression of downregulated epigenetic-related genes was highly correlated with the nicotinamide treatment,indicating a common regulation.Our results support an earlier hypothesis regarding a potential role of nicotinamide as a defense-signal mediator.
