Epigenomes最新文献_第6页

Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress. 当静脉内皮暴露于振荡剪切应力时，静脉壁细胞层的全表观基因组变化。

IF 2.5

Epigenomes Pub Date : 2023-03-20 DOI: 10.3390/epigenomes7010008

Mariya A Smetanina, Valeria A Korolenya, Alexander E Kel, Ksenia S Sevostyanova, Konstantin A Gavrilov, Andrey I Shevela, Maxim L Filipenko

{"title":"Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress.","authors":"Mariya A Smetanina, Valeria A Korolenya, Alexander E Kel, Ksenia S Sevostyanova, Konstantin A Gavrilov, Andrey I Shevela, Maxim L Filipenko","doi":"10.3390/epigenomes7010008","DOIUrl":"https://doi.org/10.3390/epigenomes7010008","url":null,"abstract":"Epigenomic changes in the venous cells exerted by oscillatory shear stress towards the endothelium may result in consolidation of gene expression alterations upon vein wall remodeling during varicose transformation. We aimed to reveal such epigenome-wide methylation changes. Primary culture cells were obtained from non-varicose vein segments left after surgery of 3 patients by growing the cells in selective media after magnetic immunosorting. Endothelial cells were either exposed to oscillatory shear stress or left at the static condition. Then, other cell types were treated with preconditioned media from the adjacent layer's cells. DNA isolated from the harvested cells was subjected to epigenome-wide study using Illumina microarrays followed by data analysis with GenomeStudio (Illumina), Excel (Microsoft), and Genome Enhancer (geneXplain) software packages. Differential (hypo-/hyper-) methylation was revealed for each cell layer's DNA. The most targetable master regulators controlling the activity of certain transcription factors regulating the genes near the differentially methylated sites appeared to be the following: (1) HGS, PDGFB, and AR for endothelial cells; (2) HGS, CDH2, SPRY2, SMAD2, ZFYVE9, and P2RY1 for smooth muscle cells; and (3) WWOX, F8, IGF2R, NFKB1, RELA, SOCS1, and FXN for fibroblasts. Some of the identified master regulators may serve as promising druggable targets for treating varicose veins in the future.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9204662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemical Inhibitors Targeting the Histone Lysine Demethylase Families with Potential for Drug Discovery. 靶向组蛋白赖氨酸去甲基酶家族的化学抑制剂与潜在的药物发现。

IF 2.5

Epigenomes Pub Date : 2023-03-11 DOI: 10.3390/epigenomes7010007

Nando Dulal Das, Hideaki Niwa, Takashi Umehara

引用次数: 1

Epigenetic Regulation in Breast Cancer: Insights on Epidrugs. 乳腺癌的表观遗传调控:外源性药物的见解。

IF 2.5

Epigenomes Pub Date : 2023-02-18 DOI: 10.3390/epigenomes7010006

Ayoung Kim, Kyumin Mo, Hyeonseok Kwon, Soohyun Choe, Misung Park, Woori Kwak, Hyunho Yoon

{"title":"Epigenetic Regulation in Breast Cancer: Insights on Epidrugs.","authors":"Ayoung Kim, Kyumin Mo, Hyeonseok Kwon, Soohyun Choe, Misung Park, Woori Kwak, Hyunho Yoon","doi":"10.3390/epigenomes7010006","DOIUrl":"https://doi.org/10.3390/epigenomes7010006","url":null,"abstract":"Breast cancer remains a common cause of cancer-related death in women. Therefore, further studies are necessary for the comprehension of breast cancer and the revolution of breast cancer treatment. Cancer is a heterogeneous disease that results from epigenetic alterations in normal cells. Aberrant epigenetic regulation is strongly associated with the development of breast cancer. Current therapeutic approaches target epigenetic alterations rather than genetic mutations due to their reversibility. The formation and maintenance of epigenetic changes depend on specific enzymes, including DNA methyltransferases and histone deacetylases, which are promising targets for epigenetic-based therapy. Epidrugs target different epigenetic alterations, including DNA methylation, histone acetylation, and histone methylation, which can restore normal cellular memory in cancerous diseases. Epigenetic-targeted therapy using epidrugs has anti-tumor effects on malignancies, including breast cancer. This review focuses on the importance of epigenetic regulation and the clinical implications of epidrugs in breast cancer.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10786447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

SNCA Gene Methylation in Parkinson's Disease and Multiple System Atrophy. SNCA基因甲基化在帕金森病和多系统萎缩中的作用

IF 2.5

Epigenomes Pub Date : 2023-02-06 DOI: 10.3390/epigenomes7010005

Ekaterina Yu Fedotova, Elena V Iakovenko, Natalia Yu Abramycheva, Sergey N Illarioshkin

{"title":"SNCA Gene Methylation in Parkinson's Disease and Multiple System Atrophy.","authors":"Ekaterina Yu Fedotova, Elena V Iakovenko, Natalia Yu Abramycheva, Sergey N Illarioshkin","doi":"10.3390/epigenomes7010005","DOIUrl":"https://doi.org/10.3390/epigenomes7010005","url":null,"abstract":"In recent years, epigenetic mechanisms have been implicated in the development of multifactorial diseases including neurodegenerative disorders. In Parkinson's disease (PD), as a synucleinopathy, most studies focused on DNA methylation of SNCA gene coding alpha-synuclein but obtained results were rather contradictory. In another neurodegenerative synucleinopathy, multiple system atrophy (MSA), very few studies investigated the epigenetic regulation. This study included patients with PD (n = 82), patients with MSA (n = 24), and a control group (n = 50). In three groups, methylation levels of CpG and non-CpG sites in regulatory regions of the SNCA gene were analyzed. We revealed hypomethylation of CpG sites in the SNCA intron 1 in PD and hypermethylation of predominantly non-CpG sites in the SNCA promoter region in MSA. In PD patients, hypomethylation in the intron 1 was associated with earlier age at the disease onset. In MSA patients, hypermethylation in the promotor was associated with shorter disease duration (before examination). These results showed different patterns of the epigenetic regulation in two synucleinopathies-PD and MSA.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9313046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

DNA Methylation Is a Potential Biomarker for Cardiometabolic Health in Mexican Children and Adolescents. DNA 甲基化是墨西哥儿童和青少年心脏代谢健康的潜在生物标志物。

IF 2.5

Epigenomes Pub Date : 2023-02-03 DOI: 10.3390/epigenomes7010004

Abeer A Aljahdali, Jaclyn M Goodrich, Dana C Dolinoy, Hyungjin M Kim, Edward A Ruiz-Narváez, Ana Baylin, Alejandra Cantoral, Libni A Torres-Olascoaga, Martha M Téllez-Rojo, Karen E Peterson

{"title":"DNA Methylation Is a Potential Biomarker for Cardiometabolic Health in Mexican Children and Adolescents.","authors":"Abeer A Aljahdali, Jaclyn M Goodrich, Dana C Dolinoy, Hyungjin M Kim, Edward A Ruiz-Narváez, Ana Baylin, Alejandra Cantoral, Libni A Torres-Olascoaga, Martha M Téllez-Rojo, Karen E Peterson","doi":"10.3390/epigenomes7010004","DOIUrl":"10.3390/epigenomes7010004","url":null,"abstract":"DNA methylation (DNAm) is a plausible mechanism underlying cardiometabolic abnormalities, but evidence is limited among youth. This analysis included 410 offspring of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort followed up to two time points in late childhood/adolescence. At Time 1, DNAm was quantified in blood leukocytes at long interspersed nuclear elements (LINE-1), H19, and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), and at Time 2 in peroxisome proliferator-activated receptor alpha (PPAR-α). At each time point, cardiometabolic risk factors were assessed including lipid profiles, glucose, blood pressure, and anthropometry. Linear mixed effects models were used for LINE-1, H19, and 11β-HSD-2 to account for the repeated-measure outcomes. Linear regression models were conducted for the cross-sectional association between PPAR-α with the outcomes. DNAm at LINE-1 was associated with log glucose at site 1 [β = -0.029, p = 0.0006] and with log high-density lipoprotein cholesterol at site 3 [β = 0.063, p = 0.0072]. 11β-HSD-2 DNAm at site 4 was associated with log glucose (β = -0.018, p = 0.0018). DNAm at LINE-1 and 11β-HSD-2 was associated with few cardiometabolic risk factors among youth in a locus-specific manner. These findings underscore the potential for epigenetic biomarkers to increase our understanding of cardiometabolic risk earlier in life.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9581475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acknowledgment to the Reviewers of Epigenomes in 2022. 向表观基因组审稿人致谢。

IF 2.5

Epigenomes Pub Date : 2023-01-13 DOI: 10.3390/epigenomes7010003

Epigenomes Editorial Office

引用次数: 0

Sex-Specific miRNA Differences in Liquid Biopsies from Subjects with Solid Tumors and Healthy Controls. 实体肿瘤患者和健康对照者液体活检中性别特异性miRNA差异

IF 2.5

Epigenomes Pub Date : 2023-01-10 DOI: 10.3390/epigenomes7010002

Elena Tomeva, Ulrike D B Krammer, Olivier J Switzeny, Alexander G Haslberger, Berit Hippe

{"title":"Sex-Specific miRNA Differences in Liquid Biopsies from Subjects with Solid Tumors and Healthy Controls.","authors":"Elena Tomeva, Ulrike D B Krammer, Olivier J Switzeny, Alexander G Haslberger, Berit Hippe","doi":"10.3390/epigenomes7010002","DOIUrl":"https://doi.org/10.3390/epigenomes7010002","url":null,"abstract":"Dysregulation of epigenetic mechanisms has been recognized to play a crucial role in cancer development, but these mechanisms vary between sexes. Therefore, we focused on sex-specific differences in the context of cancer-based data from a recent study. A total of 12 cell-free DNA methylation targets in CpG-rich promoter regions and 48 miRNAs were analyzed by qPCR in plasma samples from 8 female and 7 male healthy controls as well as 48 female and 80 male subjects with solid tumors of the bladder, brain, colorectal region (CRC), lung, stomach, pancreas, and liver. Due to the small sample size in some groups and/or the non-balanced distribution of men and women, sex-specific differences were evaluated statistically only in healthy subjects, CRC, stomach or pancreas cancer patients, and all cancer subjects combined (n female/male-8/7, 14/14, 8/15, 6/6, 48/80, respectively). Several miRNAs with opposing expressions between the sexes were observed for healthy subjects (miR-17-5p, miR-26b-5p); CRC patients (miR-186-5p, miR-22-3p, miR-22-5p, miR-25-3p, miR-92a-3p, miR-16-5p); stomach cancer patients (miR-133a-3p, miR-22-5p); and all cancer patients combined (miR-126-3p, miR-21-5p, miR-92a-3p, miR-183-5p). Moreover, sex-specific correlations that were dependent on cancer stage were observed in women (miR-27a-3p) and men (miR-17-5p, miR-20a-5p). Our results indicate the complex and distinct role of epigenetic regulation, particularly miRNAs, depending not only on the health status but also on the sex of the patient. The same miRNAs could have diverse effects in different tissues and opposing effects between the biological sexes, which should be considered in biomarker research.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10547893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Environmental Adaptation of Genetically Uniform Organisms with the Help of Epigenetic Mechanisms-An Insightful Perspective on Ecoepigenetics. 遗传均一生物在表观遗传机制下的环境适应——生态表观遗传学的一个深刻见解。

IF 2.5

Epigenomes Pub Date : 2022-12-26 DOI: 10.3390/epigenomes7010001

Günter Vogt

{"title":"Environmental Adaptation of Genetically Uniform Organisms with the Help of Epigenetic Mechanisms-An Insightful Perspective on Ecoepigenetics.","authors":"Günter Vogt","doi":"10.3390/epigenomes7010001","DOIUrl":"10.3390/epigenomes7010001","url":null,"abstract":"Organisms adapt to different environments by selection of the most suitable phenotypes from the standing genetic variation or by phenotypic plasticity, the ability of single genotypes to produce different phenotypes in different environments. Because of near genetic identity, asexually reproducing populations are particularly suitable for the investigation of the potential and molecular underpinning of the latter alternative in depth. Recent analyses on the whole-genome scale of differently adapted clonal animals and plants demonstrated that epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNAs are among the molecular pathways supporting phenotypic plasticity and that epigenetic variation is used to stably adapt to different environments. Case studies revealed habitat-specific epigenetic fingerprints that were maintained over subsequent years pointing at the existence of epigenetic ecotypes. Environmentally induced epimutations and corresponding gene expression changes provide an ideal means for fast and directional adaptation to changing or new conditions, because they can synchronously alter phenotypes in many population members. Because microorganisms inclusive of human pathogens also exploit epigenetically mediated phenotypic variation for environmental adaptation, this phenomenon is considered a universal biological principle. The production of different phenotypes from the same DNA sequence in response to environmental cues by epigenetic mechanisms also provides a mechanistic explanation for the \"general-purpose genotype hypothesis\" and the \"genetic paradox of invasions\".","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9184363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Promoter-Adjacent DNA Hypermethylation Can Downmodulate Gene Expression: TBX15 in the Muscle Lineage. 启动子邻近DNA超甲基化可以下调肌肉谱系中TBX15基因的表达。

IF 2.5

Epigenomes Pub Date : 2022-12-09 DOI: 10.3390/epigenomes6040043

Kenneth C Ehrlich, Michelle Lacey, Carl Baribault, Sagnik Sen, Pierre Olivier Esteve, Sriharsa Pradhan, Melanie Ehrlich

{"title":"Promoter-Adjacent DNA Hypermethylation Can Downmodulate Gene Expression: TBX15 in the Muscle Lineage.","authors":"Kenneth C Ehrlich, Michelle Lacey, Carl Baribault, Sagnik Sen, Pierre Olivier Esteve, Sriharsa Pradhan, Melanie Ehrlich","doi":"10.3390/epigenomes6040043","DOIUrl":"https://doi.org/10.3390/epigenomes6040043","url":null,"abstract":"TBX15, which encodes a differentiation-related transcription factor, displays promoter-adjacent DNA hypermethylation in myoblasts and skeletal muscle (psoas) that is absent from non-expressing cells in other lineages. By whole-genome bisulfite sequencing (WGBS) and enzymatic methyl-seq (EM-seq), these hypermethylated regions were found to border both sides of a constitutively unmethylated promoter. To understand the functionality of this DNA hypermethylation, we cloned the differentially methylated sequences (DMRs) in CpG-free reporter vectors and tested them for promoter or enhancer activity upon transient transfection. These cloned regions exhibited strong promoter activity and, when placed upstream of a weak promoter, strong enhancer activity specifically in myoblast host cells. In vitro CpG methylation targeted to the DMR sequences in the plasmids resulted in 86−100% loss of promoter or enhancer activity, depending on the insert sequence. These results as well as chromatin epigenetic and transcription profiles for this gene in various cell types support the hypothesis that DNA hypermethylation immediately upstream and downstream of the unmethylated promoter region suppresses enhancer/extended promoter activity, thereby downmodulating, but not silencing, expression in myoblasts and certain kinds of skeletal muscle. This promoter-border hypermethylation was not found in cell types with a silent TBX15 gene, and these cells, instead, exhibit repressive chromatin in and around the promoter. TBX18, TBX2, TBX3 and TBX1 display TBX15-like hypermethylated DMRs at their promoter borders and preferential expression in myoblasts. Therefore, promoter-adjacent DNA hypermethylation for downmodulating transcription to prevent overexpression may be used more frequently for transcription regulation than currently appreciated.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9082504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

RINGs, DUBs and Abnormal Brain Growth-Histone H2A Ubiquitination in Brain Development and Disease. 环，dub和异常脑生长-组蛋白H2A泛素化在脑发育和疾病。

IF 2.5

Epigenomes Pub Date : 2022-12-02 DOI: 10.3390/epigenomes6040042

Lucy Anne Doyle, Firuze Unlu Bektas, Eleftheria Chatzantonaki, Charlotte Repton, Alexandra Derrien, Robert Scott Illingworth

{"title":"RINGs, DUBs and Abnormal Brain Growth-Histone H2A Ubiquitination in Brain Development and Disease.","authors":"Lucy Anne Doyle, Firuze Unlu Bektas, Eleftheria Chatzantonaki, Charlotte Repton, Alexandra Derrien, Robert Scott Illingworth","doi":"10.3390/epigenomes6040042","DOIUrl":"https://doi.org/10.3390/epigenomes6040042","url":null,"abstract":"During mammalian neurodevelopment, signaling pathways converge upon transcription factors (TFs) to establish appropriate gene expression programmes leading to the production of distinct neural and glial cell types. This process is partially regulated by the dynamic modulation of chromatin states by epigenetic systems, including the polycomb group (PcG) family of co-repressors. PcG proteins form multi-subunit assemblies that sub-divide into distinct, yet functionally related families. Polycomb repressive complexes 1 and 2 (PRC1 and 2) modify the chemical properties of chromatin by covalently modifying histone tails via H2A ubiquitination (H2AK119ub1) and H3 methylation, respectively. In contrast to the PRCs, the Polycomb repressive deubiquitinase (PR-DUB) complex removes H2AK119ub1 from chromatin through the action of the C-terminal hydrolase BAP1. Genetic screening has identified several PcG mutations that are causally associated with a range of congenital neuropathologies associated with both localised and/or systemic growth abnormalities. As PRC1 and PR-DUB hold opposing functions to control H2AK119ub1 levels across the genome, it is plausible that such neurodevelopmental disorders arise through a common mechanism. In this review, we will focus on advancements regarding the composition and opposing molecular functions of mammalian PRC1 and PR-DUB, and explore how their dysfunction contributes to the emergence of neurodevelopmental disorders.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10771806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1