Epigenomes最新文献_第7页

Dynamic 5-Hydroxymethylcytosine Change: Implication for Aging of Non-Human Primate Brain. 5-羟甲基胞嘧啶的动态变化:对非人类灵长类大脑衰老的影响。

IF 2.5

Epigenomes Pub Date : 2022-11-28 DOI: 10.3390/epigenomes6040041

Xiaodong Liu, Xiao-Jiang Li, Li Lin

引用次数: 0

Regulation of Polyhomeotic Condensates by Intrinsically Disordered Sequences That Affect Chromatin Binding. 影响染色质结合的内在无序序列对多同质凝聚物的调控。

IF 2.5

Epigenomes Pub Date : 2022-11-03 DOI: 10.3390/epigenomes6040040

Ibani Kapur, Elodie L Boulier, Nicole J Francis

{"title":"Regulation of Polyhomeotic Condensates by Intrinsically Disordered Sequences That Affect Chromatin Binding.","authors":"Ibani Kapur, Elodie L Boulier, Nicole J Francis","doi":"10.3390/epigenomes6040040","DOIUrl":"https://doi.org/10.3390/epigenomes6040040","url":null,"abstract":"The Polycomb group (PcG) complex PRC1 localizes in the nucleus in condensed structures called Polycomb bodies. The PRC1 subunit Polyhomeotic (Ph) contains an oligomerizing sterile alpha motif (SAM) that is implicated in both PcG body formation and chromatin organization in Drosophila and mammalian cells. A truncated version of Ph containing the SAM (mini-Ph) forms phase-separated condensates with DNA or chromatin in vitro, suggesting that PcG bodies may form through SAM-driven phase separation. In cells, Ph forms multiple small condensates, while mini-Ph typically forms a single large nuclear condensate. We therefore hypothesized that sequences outside of mini-Ph, which are predicted to be intrinsically disordered, are required for proper condensate formation. We identified three distinct low-complexity regions in Ph based on sequence composition. We systematically tested the role of each of these sequences in Ph condensates using live imaging of transfected Drosophila S2 cells. Each sequence uniquely affected Ph SAM-dependent condensate size, number, and morphology, but the most dramatic effects occurred when the central, glutamine-rich intrinsically disordered region (IDR) was removed, which resulted in large Ph condensates. Like mini-Ph condensates, condensates lacking the glutamine-rich IDR excluded chromatin. Chromatin fractionation experiments indicated that the removal of the glutamine-rich IDR reduced chromatin binding and that the removal of either of the other IDRs increased chromatin binding. Our data suggest that all three IDRs, and functional interactions among them, regulate Ph condensate size and number. Our results can be explained by a model in which tight chromatin binding by Ph IDRs antagonizes Ph SAM-driven phase separation. Our observations highlight the complexity of regulation of biological condensates housed in single proteins.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9680516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10318017","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

Centromere Chromatin Dynamics at a Glance. 着丝粒染色质动力学概览。

IF 2.5

Epigenomes Pub Date : 2022-11-03 DOI: 10.3390/epigenomes6040039

Shivangi Shukla, Ashutosh Kumar

{"title":"Centromere Chromatin Dynamics at a Glance.","authors":"Shivangi Shukla, Ashutosh Kumar","doi":"10.3390/epigenomes6040039","DOIUrl":"https://doi.org/10.3390/epigenomes6040039","url":null,"abstract":"The centromere is a specialized DNA locus that ensures the faithful segregation of chromosomes during cell division. It does so by directing the assembly of an essential proteinaceous structure called the kinetochore. The centromere identity is primarily epigenetically defined by a nucleosome containing an H3 variant called CENP-A as well as by the interplay of several factors such as differential chromatin organization driven by CENP-A and H2A.Z, centromere-associated proteins, and post-translational modifications. At the centromere, CENP-A is not just a driving force for kinetochore assembly but also modifies the structural and dynamic properties of the centromeric chromatin, resulting in a distinctive chromatin organization. An additional level of regulation of the centromeric chromatin conformation is provided by post-translational modifications of the histones in the CENP-A nucleosomes. Further, H2A.Z is present in the regions flanking the centromere for heterochromatinization. In this review, we focus on the above-mentioned factors to describe how they contribute to the organization of the centromeric chromatin: CENP-A at the core centromere, post-translational modifications that decorate CENP-A, and the variant H2A.Z.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9680212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10322684","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

Pan HDACi Valproic Acid and Trichostatin A Show Apparently Contrasting Inflammatory Responses in Cultured J774A.1 Macrophages. 丙戊酸和曲古霉素A在培养的j774a中表现出明显不同的炎症反应1巨噬细胞。

IF 2.5

Epigenomes Pub Date : 2022-11-03 DOI: 10.3390/epigenomes6040038

Ubah Dominic Babah Ubah, Korawin Triyasakorn, Brandon Roan, Minsyusheen Conlin, James C K Lai, Prabha S Awale

{"title":"Pan HDACi Valproic Acid and Trichostatin A Show Apparently Contrasting Inflammatory Responses in Cultured J774A.1 Macrophages.","authors":"Ubah Dominic Babah Ubah, Korawin Triyasakorn, Brandon Roan, Minsyusheen Conlin, James C K Lai, Prabha S Awale","doi":"10.3390/epigenomes6040038","DOIUrl":"https://doi.org/10.3390/epigenomes6040038","url":null,"abstract":"This study was initiated as an attempt to clarify some of the apparent conflicting data regarding the so-called anti-inflammatory versus proinflammatory properties of histone deacetylase inhibitors (HDACis). In cell culture, typically, chronic pretreatment with the HDACi valproic acid (VPA) and trichostatin A (TSA) exhibits an anti-inflammatory effect. However, the effect of acute treatment with VPA and TSA on the levels of inflammatory cytokines in J774A.1 macrophage cell line is unknown. Therefore, this study investigated the effect of acute treatment with VPA and TSA on levels of key inflammatory cytokines in maximally stimulated J774A.1 cells. J774A.1 macrophages were treated with either VPA or TSA for 1 h (acute treatment), followed by maximal stimulation with LPS + IFNγ for 24 h. ELISA was used to measure the levels of proinflammatory cytokines TNFα, NO and IL-1β from the culture medium. Acute treatment with VPA showed a dose-dependent increase in levels of all three cytokines. Similar to VPA, TSA also showed a dose-dependent increase in levels of IL-1β alone. This study sheds new light on the conflicting data in the literature that may partly be explained by acute or short-term exposure versus chronic or long-term exposure to HDACi.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9680436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10318023","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

Modulation of DNA Methylation/Demethylation Reactions Induced by Nutraceuticals and Pollutants of Exposome Can Promote a C > T Mutation in the Breast Cancer Predisposing Gene PALB2 营养药品和暴露体污染物诱导的DNA甲基化/去甲基化反应的调节可促进乳腺癌易感基因PALB2的C > T突变

IF 2.5

Epigenomes Pub Date : 2022-09-30 DOI: 10.3390/epigenomes6040032

Florestan Courant, Gwenola Bougras-Cartron, Caroline Abadie, Jean-Sébastien Frenel, Pierre-François Cartron

{"title":"Modulation of DNA Methylation/Demethylation Reactions Induced by Nutraceuticals and Pollutants of Exposome Can Promote a C > T Mutation in the Breast Cancer Predisposing Gene PALB2","authors":"Florestan Courant, Gwenola Bougras-Cartron, Caroline Abadie, Jean-Sébastien Frenel, Pierre-François Cartron","doi":"10.3390/epigenomes6040032","DOIUrl":"https://doi.org/10.3390/epigenomes6040032","url":null,"abstract":"Background: Deregulation of DNA methylation/demethylation reactions may be the source of C > T mutation via active deamination of 5-methylcytosine to thymine. Exposome, that is to say, the totality of exposures to which an individual is subjected during their life, can deregulate these reactions. Thus, one may wonder whether the exposome can induce C > T mutations in the breast cancer-predisposing gene PALB2. Methods: Our work is based on the exposure of MCF10A mammary epithelial cells to seven compounds of our exposome (folate, Diuron, glyphosate, PFOA, iron, zinc, and ascorbic acid) alone or in cocktail. The qMSRE and RMS techniques were used to study the impact of these exposures on the level of methylation and mutation of the PALB2 gene. Results: Here, we have found that exposome compounds (nutriments, ions, pollutants) promoting the cytosine methylation and the 5-methylcytosine deamination have the ability to promote a specific C > T mutation in the PALB2 gene. Interestingly, we also noted that the addition of exposome compounds promoting the TET-mediated conversion of 5-methylcytosine (Ascorbic acid and iron) abrogates the presence of C > T mutation in the PALB2 gene. Conclusions: Our study provides a proof of concept supporting the idea that exposomes can generate genetic mutation by affecting DNA methylation/demethylation.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9590087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9127105","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

DNA Hypomethylation May Contribute to Metabolic Recovery of Frozen Wood Frog Brains. DNA低甲基化可能有助于冷冻林蛙大脑的代谢恢复。

IF 2.5

Epigenomes Pub Date : 2022-07-12 DOI: 10.3390/epigenomes6030017

Tighe Bloskie, Kenneth B Storey

{"title":"DNA Hypomethylation May Contribute to Metabolic Recovery of Frozen Wood Frog Brains.","authors":"Tighe Bloskie, Kenneth B Storey","doi":"10.3390/epigenomes6030017","DOIUrl":"https://doi.org/10.3390/epigenomes6030017","url":null,"abstract":"Transcriptional suppression is characteristic of extreme stress responses, speculated to preserve energetic resources in the maintenance of hypometabolism. In recent years, epigenetic regulation has become heavily implicated in stress adaptation of many animals, including supporting freeze tolerance of the wood frog (Rana sylvatica). However, nervous tissues are frequently lacking in these multi-tissue analyses which warrants investigation. The present study examines the role of DNA methylation, a core epigenetic mechanism, in the response of wood frog brains to freezing. We use immunoblot analysis to track the relative expression of DNA methyltransferases (DNMT), methyl-CpG-binding domain (MBD) proteins and ten-eleven-translocation (TET) demethylases across the freeze-thaw cycle in R. sylvatica brain, including selected comparisons to freeze-associated sub-stresses (anoxia and dehydration). Global methyltransferase activities and 5-hmC content were also assessed. The data show coordinated evidence for DNA hypomethylation in wood frog brains during freeze-recovery through the combined roles of depressed DNMT3A/3L expression driving lowered DNMT activity and increased TET2/3 levels leading to elevated 5-hmC genomic content (p < 0.05). Raised levels of DNMT1 during high dehydration were also noteworthy. The above suggest that alleviation of transcriptionally repressive 5-mC DNA methylation is a necessary component of the wood frog freeze-thaw cycle, potentially facilitating the resumption of a normoxic transcriptional state as frogs thaw and resume normal metabolic activities.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9419109","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

Epigenetic Signatures of Centrosomes Are Novel Targets in Cancer Diagnosis: Insights from an Analysis of the Cancer Genome Atlas. 中心体的表观遗传特征是癌症诊断的新目标：癌症基因组图谱分析的启示。

IF 2.5

Epigenomes Pub Date : 2022-06-02 DOI: 10.3390/epigenomes6020014

Zhou Zhang, Wei Zhang

{"title":"Epigenetic Signatures of Centrosomes Are Novel Targets in Cancer Diagnosis: Insights from an Analysis of the Cancer Genome Atlas.","authors":"Zhou Zhang, Wei Zhang","doi":"10.3390/epigenomes6020014","DOIUrl":"10.3390/epigenomes6020014","url":null,"abstract":"The centrosome plays a central role for cellular signaling and is critical for several fundamental cellular processes in human cells. Centrosome abnormalities have been linked to multiple solid tumors and hematological malignancies. We sought to explore the potential role of the DNA methylation, a critical epigenetic modification, of centrosome-related genes in different cancers. The 450K array DNA methylation data and RNA-seq data were downloaded for ~4000 tumor samples and ~500 normal controls from The Cancer Genome Atlas (TCGA) project, covering 11 major cancer types. Cancers with more than 30 normal controls were retained for analysis. Differentially modified CpGs of centrosome genes were identified, and cancer-specific epigenetic models were developed using a machine-learning algorithm for each cancer type. The association between the methylation level of differential CpGs and the corresponding gene expression, as well as the co-localization of the differential CpGs and cis-regulatory elements were evaluated. In total, 2761 CpGs located on 160 centrosome genes for 6 cancers were included in the analysis. Cancer-specific models demonstrated a high accuracy in terms of the area under the receiver operating characteristic (ROC) curve (AUC > 0.9) in five cancers and showed tissue specificity. This study enhanced our understanding of the epigenetic mechanisms underlying the DNA methylation of centrosome-related genes in cancers, and showed the potential of these epigenetic modifications as novel cancer biomarkers.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10868163","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

Insights into Cardiovascular Defects and Cardiac Epigenome in the Context of COVID-19 COVID-19背景下心血管缺陷和心脏表观基因组的见解

IF 2.5

Epigenomes Pub Date : 2022-04-21 DOI: 10.3390/epigenomes6020013

S. Sarkar, Rwik Sen

{"title":"Insights into Cardiovascular Defects and Cardiac Epigenome in the Context of COVID-19","authors":"S. Sarkar, Rwik Sen","doi":"10.3390/epigenomes6020013","DOIUrl":"https://doi.org/10.3390/epigenomes6020013","url":null,"abstract":"Although few in number, studies on epigenome of the heart of COVID-19 patients show that epigenetic signatures such as DNA methylation are significantly altered, leading to changes in expression of several genes. It contributes to pathogenic cardiac phenotypes of COVID-19, e.g., low heart rate, myocardial edema, and myofibrillar disarray. DNA methylation studies reveal changes which likely contribute to cardiac disease through unknown mechanisms. The incidence of severe COVID-19 disease, including hospitalization, requiring respiratory support, morbidity, and mortality, is disproportionately higher in individuals with co-morbidities. This poses unprecedented strains on the global healthcare system. While their underlying conditions make patients more susceptible to severe COVID-19 disease, strained healthcare systems, lack of adequate support, or sedentary lifestyles from ongoing lockdowns have proved detrimental to their underlying health conditions, thus pushing them to severe risk of congenital heart disease (CHD) itself. Prophylactic vaccines against COVID-19 have ushered new hope for CHD. A common connection between COVID-19 and CHD is SARS-CoV-2’s host receptor ACE2, because ACE2 regulates and protects organs, including the heart, in various ways. ACE2 is a common therapeutic target against cardiovascular disease and COVID-19 which damages organs. Hence, this review explores the above regarding CHDs, cardiovascular damage, and cardiac epigenetics, in COVID-19 patients.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46205557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

The Transmission of Intergenerational Epigenetic Information by Sperm microRNAs. 精子微RNA的表观遗传信息代际传递

IF 2.5

Epigenomes Pub Date : 2022-04-07 DOI: 10.3390/epigenomes6020012

Grace S Lee, Colin C Conine

引用次数: 0

Sex-Specific Expression of Non-Coding RNA Fragments in Frontal Cortex, Hippocampus and Cerebellum of Rats 非编码RNA片段在大鼠额叶皮质、海马和小脑中的性别特异性表达

IF 2.5

Epigenomes Pub Date : 2022-04-02 DOI: 10.3390/epigenomes6020011

Anna Fiselier, Boseon Byeon, Y. Ilnytskyy, I. Kovalchuk, O. Kovalchuk

{"title":"Sex-Specific Expression of Non-Coding RNA Fragments in Frontal Cortex, Hippocampus and Cerebellum of Rats","authors":"Anna Fiselier, Boseon Byeon, Y. Ilnytskyy, I. Kovalchuk, O. Kovalchuk","doi":"10.3390/epigenomes6020011","DOIUrl":"https://doi.org/10.3390/epigenomes6020011","url":null,"abstract":"Non-coding RNA fragments (ncRFs) are processed from various non-coding RNAs (ncRNAs), with the most abundant being those produced from tRNAs. ncRFs were reported in many animal and plant species. Many ncRFs exhibit tissue specificity or/and are affected by stress. There is, however, only a handful of reports that describe differential expression of ncRFs in the brain regions. In this work, we analyzed the abundance of ncRFs processed from four major ncRNAs, including tRNA (tRFs), snoRNA (snoRFs), snRNA (snRFs), and rRNA (rRFs) in the frontal cortex (FC), hippocampus (HIP), and cerebellum (CER) of male and female rats. We found brain-specific and sex-specific differences. Reads mapping to lincRNAs were significantly larger in CER as compared to HIP and CER, while those mapping to snRNAs and tRNA were smaller in HIP than in FC and CER. tRF reads were the most abundant among all ncRF reads, and FC had more reads than HIP and CER. Reads mapping to antisense ncRNAs were significantly larger in females than in males in FC. Additionally, males consistently had more tRF, snRF, and snoRF reads in all brain regions. rRFs were more abundant in males in FC and females in HIP. Several tRFs were significantly underrepresented, including tRF-ValCAC, tRF-ValACC, and tRF-LysCTT in all brain regions. We also found brain- and sex-specific differences in the number of brain function-related mRNA targets. To summarize, we found sex-specific differences in the expression of several ncRNA fragments in various brain regions of healthy rats.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42833492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1