Редактирование: DNMT3B (раздел)

==Publications==

{{medline-entry
|title=Collagens and DNA methyltransferases in mare endometrosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31512314
|abstract=Inflammation and fibroproliferative diseases may be modulated by epigenetic changes. Therefore, we suggest that epigenetic mechanisms could be involved in equine endometrosis pathogenesis. DNA methylation is one of the methods to evaluate epigenetics, through the transcription of methyltransferases ([[DNMT1]], [[DNMT3A]], [[DNMT3B]]). The correlation between DNMTs and collagen (COL) transcripts was assessed for the different Kenney and Doig's (Current Therapy in Theriogenology. Philadelphia: WB Saunders; 1986) endometrium categories. Endometrial biopsies were randomly collected from cyclic mares. Histological classification (category I, n = 13; II A, n = 17; II B, n = 12; and III, n = 7) and evaluation of [[COL1A2]], [[COL3A1]] and DNMTs transcripts by qPCR, were performed. Data were analysed by one-way analysis of variance (ANOVA), Kruskal-Wallis test and Pearson correlation. As mares aged, there was an increase in endometrium fibrosis (p < .01), and in [[DNMT1]] mRNA (p < .001). Considering [[DNMT3B]] transcripts for each category, there was an increase with fibrosis (p < .05). No changes were observed for [[DNMT1]] and [[DNMT3A]] transcripts. However, [[DNMT3A]] mRNA levels were the highest in all categories (p < .01). In category I endometrium, a positive correlation was observed for transcripts of all DNMTs in both COLs (p < .01). In category IIA, this correlation was also maintained for all DNMTs transcripts in [[COL1A2]] (p < .05), but only for [[DNMT3B]] in [[COL3A1]] (p < .05). In category IIB, there was a positive correlation between [[DNMT3B]] and [[COL3A1]] (p < .05). In category III, a positive correlation was only observed between [[DNMT3B]] and [[COL3A1]] (p < .05). Our results suggest that there is a disturbance in COLs and DNMTs correlation during fibrosis.
|mesh-terms=* Aging
* Animals
* Collagen
* DNA (Cytosine-5-)-Methyltransferases
* DNA Methylation
* Endometritis
* Endometrium
* Female
* Fibrosis
* Horse Diseases
* Horses
* RNA, Messenger
|keywords=* DNA methylation
* collagen
* endometrium
* epigenetic
* fibrosis
* mare
|full-text-url=https://sci-hub.do/10.1111/rda.13515
}}
{{medline-entry
|title=Alcohol Extracts From [i]Ganoderma lucidum[/i] Delay the Progress of Alzheimer's Disease by Regulating DNA Methylation in Rodents.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30971923
|abstract=Age-related changes in methylation are involved in the occurrence and development of tumors, autoimmune disease, and nervous system disorders, including Alzheimer's disease (AD), in elderly individuals; hence, modulation of these methylation changes may be an effective strategy to delay the progression of AD pathology. In this study, the AD model rats were used to screen the main active extracts from the mushroom, [i]Ganoderma lucidum[/i], for anti-aging properties, and their effects on DNA methylation were evaluated. The results of evaluation of rats treated with 100 mg/kg/day of D-galactose to induce accelerated aging showed that alcohol extracts of [i]G. lucidum[/i] contained the main active anti-aging extract. The effects on DNA methylation of these [i]G. lucidum[/i] extracts were then evaluated using SAMP8 and APP/PS1 AD model mice by whole genome bisulfite sequencing, and some methylation regulators including Histone H3, [[DNMT3A]], and [[DNMT3B]] in brain tissues were up-regulated after treatment with alcohol extracts from [i]G. lucidum[/i]. Molecular docking analysis was carried out to screen for molecules regulated by specific components, including ganoderic acid Mk, ganoderic acid [[C6]], and lucidone A, which may be active ingredients of [i]G. lucidum[/i], including the methylation regulators of Histone H3, MYT, [[DNMT3A]], and [[DNMT3B]]. Auxiliary tests also demonstrated that [i]G. lucidum[/i] alcohol extracts could improve learning and memory function, ameliorate neuronal apoptosis and brain atrophy, and down-regulate the expression of the AD intracellular marker, Aβ . We concluded that alcohol extracts from [i]G. lucidum[/i], including ganoderic acid and lucidone A, are the main extracts involved in delaying AD progression.

|keywords=* Alzheimer’s disease
* DNA methylation
* Ganoderma lucidum
* active ingredients
* aging
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444160
}}
{{medline-entry
|title=Human iPSC-derived [[MSC]]s (i[[MSC]]s) from aged individuals acquire a rejuvenation signature.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30885246
|abstract=Primary mesenchymal stem cells ([[MSC]]s) are fraught with aging-related shortfalls. Human-induced pluripotent stem cell (iPSC)-derived [[MSC]]s (i[[MSC]]s) have been shown to be a useful clinically relevant source of [[MSC]]s that circumvent these aging-associated drawbacks. To date, the extent of the retention of aging-hallmarks in i[[MSC]]s differentiated from iPSCs derived from elderly donors remains unclear. Fetal femur-derived [[MSC]]s (f[[MSC]]s) and adult bone marrow [[MSC]]s (a[[MSC]]s) were isolated, corresponding iPSCs were generated, and i[[MSC]]s were differentiated from f[[MSC]]-iPSCs, from a[[MSC]]-iPSCs, and from human embryonic stem cells (ESCs) H1. In addition, typical [[MSC]] characterization such as cell surface marker expression, differentiation capacity, secretome profile, and trancriptome analysis were conducted for the three distinct i[[MSC]] preparations-f[[MSC]]-i[[MSC]]s, a[[MSC]]-i[[MSC]]s, and ESC-i[[MSC]]s. To verify these results, previously published data sets were used, and also, additional a[[MSC]]s and i[[MSC]]s were analyzed. f[[MSC]]s and a[[MSC]]s both express the typical [[MSC]] cell surface markers and can be differentiated into osteogenic, adipogenic, and chondrogenic lineages in vitro. However, the transcriptome analysis revealed overlapping and distinct gene expression patterns and showed that f[[MSC]]s express more genes in common with ESCs than with a[[MSC]]s. f[[MSC]]-i[[MSC]]s, a[[MSC]]-i[[MSC]]s, and ESC-i[[MSC]]s met the criteria set out for [[MSC]]s. Dendrogram analyses confirmed that the transcriptomes of all i[[MSC]]s clustered together with the parental [[MSC]]s and separated from the [[MSC]]-iPSCs and ESCs. i[[MSC]]s irrespective of donor age and cell type acquired a rejuvenation-associated gene signature, specifically, the expression of [[INHBE]], [[DNMT3B]], POU5F1P1, [[CDKN1C]], and [[GCNT2]] which are also expressed in pluripotent stem cells (iPSCs and ESC) but not in the parental a[[MSC]]s. i[[MSC]]s expressed more genes in common with f[[MSC]]s than with a[[MSC]]s. Independent real-time PCR comparing a[[MSC]]s, f[[MSC]]s, and i[[MSC]]s confirmed the differential expression of the rejuvenation (COX7A, EZA2, and TMEM119) and aging (CXADR and IGSF3) signatures. Importantly, in terms of regenerative medicine, i[[MSC]]s acquired a secretome (e.g., angiogenin, DKK-1, IL-8, PDGF-AA, osteopontin, [[SERPINE1]], and VEGF) similar to that of f[[MSC]]s and a[[MSC]]s, thus highlighting their ability to act via paracrine signaling. i[[MSC]]s irrespective of donor age and cell source acquire a rejuvenation gene signature. The i[[MSC]] concept could allow circumventing the drawbacks associated with the use of adult [[MSC]]s und thus provide a promising tool for use in various clinical settings in the future.
|mesh-terms=* Aged
* Aging
* Antigens, Differentiation
* Cell Differentiation
* Female
* Fetus
* Humans
* Induced Pluripotent Stem Cells
* Male
* Mesenchymal Stem Cells
* Middle Aged
* Transcriptome
|keywords=* Aged MSC
* Aging
* Fetal MSCs
* Rejuvenation
* Secretome
* Transcriptome
* iMSCs
* iPSCs
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423778
}}
{{medline-entry
|title=Effects of Parental Aging During Embryo Development and Adult Life: The Case of Nothobranchius furzeri.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29304310
|abstract=Studies on parental aging are a very attractive field, although it is poorly understood how parental age affects embryonic development and adult traits of the offspring. In this study, we used the turquoise killifish Nothobranchius furzeri, as is the vertebrate with shortest captive lifespan and an interesting model. The embryos of N. furzeri can follow two distinct developmental pathways either entering diapause or proceeding through direct development. Thus, this embryonic plasticity allows this model to be used to study different factors that could affect their embryonic development, including parental age. The first goal of the present study was to investigate whether parental aging could affect the embryo development. To do this, we collected F1 embryos from two breeder groups (old parents and young parents). We monitored the duration of embryonic development and analyzed genes involved in dorsalization process. The second goal was to investigate if embryonic developmental plasticity could be modulated by an epigenetic process. To this end, the expression of DNMTs genes was examined. Our data support the hypothesis that diapause, occurring more frequently in embryos from old parents, is associated with increased expression of [[DNMT3A]] and [[DNMT3B]] suggesting an epigenetic control. Finally, we analyzed whether parental age could affect metabolism and growth during adult life. Morphometric results and qPCR analysis of genes from IGF system showed a slower growth in adults from old breeders. Moreover, a gender-specificity effect on growth emerged. In conclusion, these results may contribute to the better understanding of the complex mechanism of aging.
|mesh-terms=* Aging
* Animals
* Cyprinodontiformes
* Embryo, Nonmammalian
* Embryonic Development
* Epigenesis, Genetic
* Fish Proteins
* Gene Expression Regulation, Developmental
* Longevity
|keywords=* IGF system
* diapause
* embryo development plasticity
* killifish
* transgenerational effects
|full-text-url=https://sci-hub.do/10.1089/zeb.2017.1494
}}
{{medline-entry
|title=Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons from Adult Common Marmoset Fibroblasts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28635509
|abstract=The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter life span compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties, including the development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers. In addition, expression of key pluripotency genes (ZFP42, [[PODXL]], [[DNMT3B]], C-[[MYC]], LIN28, [[KLF4]], [[NANOG]], [[SOX2]], and OCT4) was observed. We then tested the neural differentiation capacity and gene expression profiles of Cj-iPSCs and a marmoset embryonic stem cell line (Cj-ESC) after dual-SMAD inhibition. Exposure to CHIR99021 and sonic hedgehog (SHH) for 12 and 16 days, respectively, patterned the cells toward a ventralized midbrain dopaminergic phenotype, confirmed by expression of [[FOXA2]], [[OTX2]], EN-1, and tyrosine hydroxylase. These results demonstrate that common marmoset stem cells will be able to serve as a platform for investigating regenerative medicine approaches targeting the dopaminergic system.
|mesh-terms=* Aging
* Animals
* Callithrix
* Cell Differentiation
* Cell Lineage
* Dopaminergic Neurons
* Fibroblasts
* Gene Expression Regulation
* Induced Pluripotent Stem Cells
* Mesencephalon
|keywords=* Parkinson's disease
* induced pluripotent stem cells
* neural differentiation
* nonhuman primate model
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576272
}}
{{medline-entry
|title=Forkhead box A2 regulates biliary heterogeneity and senescence during cholestatic liver injury in mice‡.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27639079
|abstract=Biliary-committed progenitor cells (small mouse cholangiocytes; SMCCs) from small bile ducts are more resistant to hepatobiliary injury than large mouse cholangiocytes (LGCCs) from large bile ducts. The definitive endoderm marker, forkhead box A2 (FoxA2), is the key transcriptional factor that regulates cell differentiation and tissue regeneration. Our aim was to characterize the translational role of FoxA2 during cholestatic liver injury. Messenger RNA expression in SMCCs and LGCCs was assessed by polymerase chain reaction (PCR) array analysis. Liver tissues and hepatic stellate cells (HSCs) from primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) patients were tested by real-time PCR for methylation, senescence, and fibrosis markers. Bile duct ligation (BDL) and multidrug resistance protein 2 (MDR2) knockout mice (MDR2  ) were used as animal models of cholestatic liver injury with or without healthy transplanted large or small cholangiocytes. We demonstrated that FoxA2 was notably enhanced in murine liver progenitor cells and SMCCs and was silenced in human PSC and PBC liver tissues relative to respective controls that are correlated with the epigenetic methylation enzymes, DNA methyltransferase (DNMT) 1 and [[DNMT3B]]. Serum alanine aminotransferase and aspartate aminotransferase levels in nonobese diabetic/severe combined immunodeficiency mice engrafted with SMCCs post-BDL showed significant changes compared to vehicle-treated mice, along with improved liver fibrosis. Enhanced expression of FoxA2 was observed in BDL mouse liver after SMCC cell therapy. Furthermore, activation of fibrosis signaling pathways were observed in BDL/MDR2  mouse liver as well as in isolated HSCs by laser capture microdissection, and these signals were recovered along with reduced hepatic senescence and enhanced hepatic stellate cellular senescence after SMCC engraft. The definitive endoderm marker and the positive regulator of biliary development, FoxA2, mediates the therapeutic effect of biliary-committed progenitor cells during cholestatic liver injury. (Hepatology 2017;65:544-559).
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Animals
* Bile Ducts
* Cell Communication
* Cholestasis
* Disease Models, Animal
* Down-Regulation
* Gene Expression Regulation
* Genetic Heterogeneity
* Hepatic Stellate Cells
* Hepatocyte Nuclear Factor 3-beta
* Hepatocytes
* Humans
* Liver
* Mice
* Mice, Knockout
* Middle Aged
* Real-Time Polymerase Chain Reaction
* Sampling Studies

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5258713
}}
{{medline-entry
|title=Age-dependent expression of [[DNMT1]] and [[DNMT3B]] in PBMCs from a large European population enrolled in the MARK-AGE study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27169697
|abstract=Aging is associated with alterations in the content and patterns of DNA methylation virtually throughout the entire human lifespan. Reasons for these variations are not well understood. However, several lines of evidence suggest that the epigenetic instability in aging may be traced back to the alteration of the expression of DNA methyltransferases. Here, the association of the expression of DNA methyltransferases [[DNMT1]] and [[DNMT3B]] with age has been analysed in the context of the MARK-AGE study, a large-scale cross-sectional study of the European general population. Using peripheral blood mononuclear cells, we assessed the variation of [[DNMT1]] and [[DNMT3B]] gene expression in more than two thousand age-stratified women and men (35-75 years) recruited across eight European countries. Significant age-related changes were detected for both transcripts. The level of [[DNMT1]] gradually dropped with aging but this was only observed up to the age of 64 years. By contrast, the expression of [[DNMT3B]] decreased linearly with increasing age and this association was particularly evident in females. We next attempted to trace the age-related changes of both transcripts to the influence of different variables that have an impact on changes of their expression in the population, including demographics, dietary and health habits, and clinical parameters. Our results indicate that age affects the expression of [[DNMT1]] and [[DNMT3B]] as an almost independent variable in respect of all other variables evaluated.
|mesh-terms=* Adult
* Aged
* Aging
* Body Mass Index
* DNA (Cytosine-5-)-Methyltransferase 1
* DNA (Cytosine-5-)-Methyltransferases
* European Continental Ancestry Group
* Female
* Gene Expression Regulation, Developmental
* Gene Expression Regulation, Enzymologic
* Gene Ontology
* Humans
* Leukocytes, Mononuclear
* Life Style
* Male
* Middle Aged
* RNA, Messenger
* Regression Analysis
* Risk Factors
|keywords=* DNA methylation
* DNMT1
* DNMT3B
* aging
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933658
}}
{{medline-entry
|title=Insight into the molecular pathophysiology of myelodysplastic syndromes: targets for novel therapy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27147278
|abstract=Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by abnormal cellular differentiation and maturation with variable progression to acute leukemia. Over the last decade, scientific discoveries have unraveled specific pathways involved in the complex pathophysiology of MDS. Prominent examples include aberrations in cytokines and their signaling pathways (such as tumor necrosis factor-alpha, interferon-gamma, SMAD proteins), mutations in genes encoding the RNA splicing machinery (SF3B1, [[SRSF2]], [[ZRSR2]], and [[U2AF1]] genes), mutations in genes disrupting the epigenetic machinery (TET2, [[DNMT3A]], [[DNMT3B]], [[EZH2]], ASXL1). In addition, abnormalities in regulatory T-cell dynamics and atypical interactions between the bone marrow microenvironment, stroma and progenitor cells, and abnormal maintenance of telomeres are also notable contributors to the complex pathogenesis of MDS. These pathways represent potential targets for novel therapies. Specific therapies include drugs targeting aberrant DNA methylation and chromatin remodeling, modulating/activating the immune system to enhance tumor-specific cellular immune responses and reduce anomalous cytokine signaling, and blocking abnormal interaction between hematopoietic progenitors and stromal cells. 
|mesh-terms=* Animals
* Bone Marrow
* Cellular Microenvironment
* Cellular Senescence
* Cytokines
* DNA Methylation
* Epigenesis, Genetic
* Gene Expression Regulation
* Gene Silencing
* Genetic Variation
* Humans
* Immune System Diseases
* Molecular Targeted Therapy
* Myelodysplastic Syndromes
* RNA Splicing
* Signal Transduction
* Stromal Cells
* Telomere
|keywords=* bone marrow microenvironment
* cellular senescence
* cytokines
* epigenetic regulation
* immune dysregulation
* myelodysplastic syndromes
* pathogenesis
* targeted therapies
* telomeric erosion
|full-text-url=https://sci-hub.do/10.1111/ejh.12771
}}
{{medline-entry
|title=The role of DNA methylation in aging, rejuvenation, and age-related disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23098078
|abstract=DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-L-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) [[DNMT3A]] and [[DNMT3B]] and are subsequently maintained by [[DNMT1]]. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation.
|mesh-terms=* Aging
* Animals
* DNA Methylation
* DNA Modification Methylases
* Epigenesis, Genetic
* Humans
* Rejuvenation

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482848
}}
{{medline-entry
|title=Differential expression of epigenetic modulators during human embryonic stem cell differentiation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18953677
|abstract=Although the progression of aging and the diseases associated with it are extensively studied, little is known about the initiation of the aging process. Telomerase is down-regulated early in embryonic differentiation, thereby contributing to telomeric attrition and aging. The mechanisms underlying this inhibition remain elusive, but epigenetic studies in differentiating human embryonic stem (hES) cells could give clues about how and when DNA methylation and histone deacetylation work together to contribute to the inactivation of hTERT, the catalytic subunit of telomerase, at the onset of the aging process. We have confirmed the differentiation status of cultured hES colonies with morphological assessment and immunohistochemical stainings for pluripotent stem cells. In hES cells with varying degrees of differentiation, we have shown a stronger association between hES differentiation and expression of the epigenetic regulators [[DNMT3A]] and [[DNMT3B]] than between genetic modulators of differentiation such as c-[[MYC]]. We also propose a new model system for analyses of stem cell regions, which are differentially down-regulating the expression of hTERT and the actions of epigenetic modulators such as the DNMTs and histone methyltransferases.
|mesh-terms=* Aging
* Alkaline Phosphatase
* Animals
* Biomarkers
* Cell Differentiation
* Cells, Cultured
* DNA (Cytosine-5-)-Methyltransferases
* Embryonic Stem Cells
* Epigenesis, Genetic
* Fibroblasts
* Fibronectins
* Gene Expression Regulation
* Histones
* Humans
* Immunohistochemistry
* Methylation
* Mice
* Microscopy, Phase-Contrast
* Proto-Oncogene Proteins c-myc
* Telomerase

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629501
}}