Olena Gruzieva, Simon Kebede Merid, Su Chen, Nandini Mukherjee, Anna M Hedman, Catarina Almqvist, Ellika Andolf, Yu Jiang, Juha Kere, Annika Scheynius, Cilla Söderhäll, Vilhelmina Ullemar, Wilfried Karmaus, Erik Melén, Syed Hasan Arshad, Göran Pershagen
{"title":"DNA Methylation Trajectories During Pregnancy.","authors":"Olena Gruzieva, Simon Kebede Merid, Su Chen, Nandini Mukherjee, Anna M Hedman, Catarina Almqvist, Ellika Andolf, Yu Jiang, Juha Kere, Annika Scheynius, Cilla Söderhäll, Vilhelmina Ullemar, Wilfried Karmaus, Erik Melén, Syed Hasan Arshad, Göran Pershagen","doi":"10.1177/2516865719867090","DOIUrl":"https://doi.org/10.1177/2516865719867090","url":null,"abstract":"<p><p>There is emerging evidence on DNA methylation (DNAm) variability over time; however, little is known about dynamics of DNAm patterns during pregnancy. We performed an epigenome-wide longitudinal DNAm study of a well-characterized sample of young women from the Swedish Born into Life study, with repeated blood sampling before, during and after pregnancy (n = 21), using the Illumina Infinium MethylationEPIC array. We conducted a replication in the Isle of Wight third-generation birth cohort (n = 27), using the Infinium HumanMethylation450k BeadChip. We identified 196 CpG sites displaying intra-individual longitudinal change in DNAm with a false discovery rate (FDR) <i>P</i> < .05. Most of these (91%) showed a decrease in average methylation levels over the studied period. We observed several genes represented by ⩾3 differentially methylated CpGs: <i>HOXB3, AVP, LOC100996291</i>, and MicroRNA 10a. Of 36 CpGs available in the replication cohort, 17 were replicated, all but 2 with the same direction of association (replication <i>P</i> < .05). Biological pathway analysis demonstrated that FDR-significant CpGs belong to genes overrepresented in metabolism-related pathways, such as adipose tissue development, regulation of insulin receptor signaling, and mammary gland fat development. These results contribute to a better understanding of the biological mechanisms underlying important physiological alterations and adaptations for pregnancy and lactation.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"12 ","pages":"2516865719867090"},"PeriodicalIF":2.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719867090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10803414","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}
{"title":"Tying Metabolic Branches With Histone Tails Using Systems Biology","authors":"S. Chandrasekaran","doi":"10.1177/2516865719869683","DOIUrl":"https://doi.org/10.1177/2516865719869683","url":null,"abstract":"Histone modifications represent an innate cellular mechanism to link nutritional status to gene expression. Metabolites such as acetyl-CoA and S-adenosyl methionine influence gene expression by serving as substrates for modification of histones. Yet, we lack a predictive model for determining histone modification levels based on cellular metabolic state. The numerous metabolic pathways that intersect with histone marks makes it highly challenging to understand their interdependencies. Here, we highlight new systems biology tools to unravel the impact of nutritional cues and metabolic fluxes on histone modifications.","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719869683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46257297","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}
Epigenetics InsightsPub Date : 2018-12-25eCollection Date: 2018-01-01DOI: 10.1177/2516865718820946
Mohamad-Ali Fawal, Alice Davy
{"title":"Impact of Metabolic Pathways and Epigenetics on Neural Stem Cells.","authors":"Mohamad-Ali Fawal, Alice Davy","doi":"10.1177/2516865718820946","DOIUrl":"https://doi.org/10.1177/2516865718820946","url":null,"abstract":"<p><p>Balancing self-renewal with differentiation is crucial for neural stem cells (NSC) functions to ensure tissue development and homeostasis. Over the last years, multiple studies have highlighted the coupling of either metabolic or epigenetic reprogramming to NSC fate decisions. Metabolites are essential as they provide the energy and building blocks for proper cell function. Moreover, metabolites can also function as substrates and/or cofactors for epigenetic modifiers. It is becoming more evident that metabolic alterations and epigenetics rewiring are highly intertwined; however, their relation regarding determining NSC fate is not well understood. In this review, we summarize the major metabolic pathways and epigenetic modifications that play a role in NSC. We then focus on the notion that nutrients availability can function as a switch to modify the epigenetic machinery and drive NSC sequential differentiation during embryonic neurogenesis.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"11 ","pages":"2516865718820946"},"PeriodicalIF":2.2,"publicationDate":"2018-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865718820946","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36839806","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}
Epigenetics InsightsPub Date : 2018-12-13eCollection Date: 2018-01-01DOI: 10.1177/2516865718818838
Claudio Mussolino
{"title":"Precise Epigenome Editing on the Stage: A Novel Approach to Modulate Gene Expression.","authors":"Claudio Mussolino","doi":"10.1177/2516865718818838","DOIUrl":"https://doi.org/10.1177/2516865718818838","url":null,"abstract":"<p><p>In the last decades, a better understanding of human pathologies has revealed that genetic alterations as well as epigenetic aberrations can be drivers of a disease or exacerbate its manifestation. The availability of customizable platforms that allow precise genomic targeting has opened the possibility to cure genetic disorders by tackling directly the origin of the disease. Indeed, tethering of different effectors to a DNA-binding moiety grants precise alterations of the genome, transcriptome, or epigenome with the aim of normalizing disease-causing aberrations. The use of designer nucleases for therapeutic genome editing is currently approaching the clinics, and safety concerns arise with respect to off-target effects. Epigenome editing might be a valuable alternative, as it does not rely on DNA double-strand breaks, one of the most deleterious form of DNA damage, to exert its function. We have recently described designer epigenome modifier (DEM), a novel platform for achieving precise epigenome editing in clinically relevant primary human cells. We discuss the efficiency of DEM and highlight their remarkable safety profile, which certainly makes this platform a valuable candidate for future clinical translation.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"11 ","pages":"2516865718818838"},"PeriodicalIF":2.2,"publicationDate":"2018-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865718818838","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36793703","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}
Epigenetics InsightsPub Date : 2018-12-12eCollection Date: 2018-01-01DOI: 10.1177/2516865718818839
Aatira Vijay, Iti Garg, Mohammad Zahid Ashraf
{"title":"Perspective: DNA Copy Number Variations in Cardiovascular Diseases.","authors":"Aatira Vijay, Iti Garg, Mohammad Zahid Ashraf","doi":"10.1177/2516865718818839","DOIUrl":"https://doi.org/10.1177/2516865718818839","url":null,"abstract":"<p><p>Human genome contains many variations, often called mutations, which are difficult to detect and have remained a challenge for years. A substantial part of the genome encompasses repeats and when such repeats are in the coding region they may lead to change in the gene expression profile followed by pathological conditions. Structural variants are alterations which change one or more sequence feature in the chromosome such as change in the copy number, rearrangements, and translocations of a sequence and can be balanced or unbalanced. Copy number variants (CNVs) may increase or decrease the copies of a given region and have a pivotal role in the onset of many diseases including cardiovascular disorders. Cardiovascular disorders have a magnitude of well-established risk factors and etiology, but their correlation with CNVs is still being studied. In this article, we have discussed history of CNVs and a summary on the diseases associated with CNVs. To detect such variations, we shed light on the number of techniques introduced so far and their limitations. The lack of studies on cardiovascular diseases to determine the frequency of such variants needs clinical studies with larger cohorts. This review is a compilation of articles suggesting the importance of CNVs in multitude of cardiovascular anomalies. Finally, future perspectives for better understanding of CNVs and cardiovascular disorders have also been discussed.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"11 ","pages":"2516865718818839"},"PeriodicalIF":2.2,"publicationDate":"2018-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865718818839","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36781978","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}
{"title":"Knowledge, Attitudes, and Practices of Women Toward Prenatal Genetic Testing.","authors":"Nour Abdo, Nadia Ibraheem, Nail Obeidat, Ashley Graboski-Bauer, Anwar Batieha, Nada Altamimi, Moawia Khatatbih","doi":"10.1177/2516865718813122","DOIUrl":"https://doi.org/10.1177/2516865718813122","url":null,"abstract":"<p><strong>Objectives: </strong>We aim to address public knowledge, attitudes, and practices relative to prenatal genetic testing as a starting point for policy development in Jordan.</p><p><strong>Study design: </strong>We conducted a cross-sectional prenatal genetic testing knowledge, attitudes, and practices survey with 1111 women recruited at obstetrics and gynecology clinics nationwide. Data were analyzed using a variety of descriptive and inferential statistical tests.</p><p><strong>Results: </strong>The overwhelming majority (>94%) of participants considered prenatal genetic testing, particularly non-invasive prenatal genetic screening, procedures to be good, comfortable, and reasonable, even when the non-diagnostic nature of non-invasive prenatal genetic screening was explained. Likewise, 95% encouraged the implementation of non-invasive prenatal genetic screening within the Jordanian health system, but most preferred it to remain optional. However, women in higher-risk age brackets, in consanguineous marriages, and with less education were significantly less interested in learning about non-invasive prenatal genetic screening. Only 60% of women interviewed were satisfied with the services provided by their obstetric/gynecologist. The more satisfied the women were, the more they are likely to adapt non-invasive prenatal genetic screening.</p><p><strong>Conclusions: </strong>In sum, although the data support the receptivity of Jordanian women to national implementation of non-invasive prenatal genetic screening, such policies should be accompanied by health education to increase the genetic literacy of the population and to engage high-risk populations. Thus, this offers rare insight into the readiness of 1 particular Arab population to adapt non-invasive prenatal genetic screening technologies.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"11 ","pages":"2516865718813122"},"PeriodicalIF":2.2,"publicationDate":"2018-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865718813122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36843332","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}
Epigenetics InsightsPub Date : 2018-11-27eCollection Date: 2018-01-01DOI: 10.1177/2516865718814543
Syed Shoeb Razvi, Hani Choudhry, Mohammed Nihal Hasan, Mohammed A Hassan, Said Salama Moselhy, Khalid Omer Abualnaja, Mazin A Zamzami, Taha Abduallah Kumosani, Abdulrahman Labeed Al-Malki, Majed A Halwani, Abdulkhaleg Ibrahim, Ali Hamiche, Christian Bronner, Tadao Asami, Mahmoud Alhosin
{"title":"Identification of Deregulated Signaling Pathways in Jurkat Cells in Response to a Novel Acylspermidine Analogue-N<sup>4</sup>-Erucoyl Spermidine.","authors":"Syed Shoeb Razvi, Hani Choudhry, Mohammed Nihal Hasan, Mohammed A Hassan, Said Salama Moselhy, Khalid Omer Abualnaja, Mazin A Zamzami, Taha Abduallah Kumosani, Abdulrahman Labeed Al-Malki, Majed A Halwani, Abdulkhaleg Ibrahim, Ali Hamiche, Christian Bronner, Tadao Asami, Mahmoud Alhosin","doi":"10.1177/2516865718814543","DOIUrl":"https://doi.org/10.1177/2516865718814543","url":null,"abstract":"<p><p>Natural polyamines such as putrescine, spermidine, and spermine are crucial in the cell proliferation and maintenance in all the eukaryotes. However, the requirement of polyamines in tumor cells is stepped up to maintain tumorigenicity. Many synthetic polyamine analogues have been designed recently to target the polyamine metabolism in tumors to induce apoptosis. N<sup>4</sup>-Erucoyl spermidine (designed as N<sup>4</sup>-Eru), a novel acylspermidine derivative, has been shown to exert selective inhibitory effects on both hematological and solid tumors, but its mechanisms of action are unknown. In this study, RNA sequencing was performed to investigate the anticancer mechanisms of N<sup>4</sup>-Eru-treated T-cell acute lymphoblastic leukemia (ALL) cell line (Jurkat cells), and gene expression was examined through different tools. We could show that many key oncogenes including <i>NDRG1, CACNA1G, TGFBR2, NOTCH1,2,3, UHRF1, DNMT1,3, HDAC1,3, KDM3A, KDM4B, KDM4C, FOS</i>, and <i>SATB1</i> were downregulated, whereas several tumor suppressor genes such as <i>CDKN2AIPNL, KISS1, DDIT3, TP53I13, PPARG, FOXP1</i> were upregulated. Data obtained through RNA-Seq further showed that N<sup>4</sup>-Eru inhibited the NOTCH/Wnt/JAK-STAT axis. This study also indicated that N<sup>4</sup>-Eru-induced apoptosis could involve several key signaling pathways in cancer. Altogether, our results suggest that N<sup>4</sup>-Eru is a promising drug to treat ALL.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"11 ","pages":"2516865718814543"},"PeriodicalIF":2.2,"publicationDate":"2018-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865718814543","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36750845","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}
Epigenetics InsightsPub Date : 2018-11-19eCollection Date: 2018-01-01DOI: 10.1177/2516865718811117
Maud de Dieuleveult, Benoit Miotto
{"title":"DNA Methylation and Chromatin: Role(s) of Methyl-CpG-Binding Protein ZBTB38.","authors":"Maud de Dieuleveult, Benoit Miotto","doi":"10.1177/2516865718811117","DOIUrl":"https://doi.org/10.1177/2516865718811117","url":null,"abstract":"<p><p>DNA methylation plays an essential role in the control of gene expression during early stages of development as well as in disease. Although many transcription factors are sensitive to this modification of the DNA, we still do not clearly understand how it contributes to the establishment of proper gene expression patterns. We discuss here the recent findings regarding the biological and molecular function(s) of the transcription factor ZBTB38 that binds methylated DNA sequences in vitro and in cells. We speculate how these findings may help understand the role of DNA methylation and DNA methylation-sensitive transcription factors in mammalian cells.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"11 ","pages":"2516865718811117"},"PeriodicalIF":2.2,"publicationDate":"2018-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865718811117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36722086","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}
Epigenetics InsightsPub Date : 2018-10-14eCollection Date: 2018-01-01DOI: 10.1177/2516865718803641
Jessica Camacho, Patrick Allard
{"title":"Histone Modifications: Epigenetic Mediators of Environmental Exposure Memory.","authors":"Jessica Camacho, Patrick Allard","doi":"10.1177/2516865718803641","DOIUrl":"10.1177/2516865718803641","url":null,"abstract":"<p><p>How organisms retain a memory of ancestral environmental exposure is a phenomenon that is still poorly understood. Recently published work by our group and others, regarding environmentally induced transgenerational effects, have identified an array of mechanisms, with a particular focus on histone modifications, that shed some light on the underlying epigenetic processes driving long-term generational effects.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"11 ","pages":"2516865718803641"},"PeriodicalIF":3.2,"publicationDate":"2018-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/54/b2/10.1177_2516865718803641.PMC6233965.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36674849","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}
Epigenetics InsightsPub Date : 2018-10-14eCollection Date: 2018-01-01DOI: 10.1177/2516865718802931
Adrian Janiszewski, Juan Song, Lotte Vanheer, Natalie De Geest, Vincent Pasque
{"title":"Dynamics of DNA Methylation Reprogramming Influenced by X Chromosome Dosage in Induced Pluripotent Stem Cells.","authors":"Adrian Janiszewski, Juan Song, Lotte Vanheer, Natalie De Geest, Vincent Pasque","doi":"10.1177/2516865718802931","DOIUrl":"https://doi.org/10.1177/2516865718802931","url":null,"abstract":"<p><p>How the epigenome of one cell type is remodeled during reprogramming into another unrelated type of cell remains unclear. Overexpression of transcription factors in somatic cells enables the induction of induced pluripotent stem cells (iPSCs). This process entails genome-wide remodeling of DNA methylation, chromatin, and transcription. Recent work suggests that the number of active X chromosomes present in a cell influences remodeling of DNA methylation during somatic cell reprogramming to mouse iPSCs. Female iPSCs with 2 active X chromosomes display global DNA hypomethylation, whereas male XY iPSCs show DNA methylation levels similar to the somatic cells they are derived from. Global DNA methylation erasure in female iPSCs takes place genome-wide and involves repression of DNA methyltransferases. However, on loss of one X chromosome, female iPSCs acquire a DNA methylation landscape resembling that of XY iPSCs. Therefore, it is the X chromosome dosage that dictates global DNA methylation levels in iPSCs. Here, we discuss the evidence that links X chromosome dosage with the regulation of DNA methylation in pluripotent stem cells. We focus on iPSCs reprogramming studies, where X chromosome status is a novel factor impacting our understanding of epigenetic remodeling.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"11 ","pages":"2516865718802931"},"PeriodicalIF":2.2,"publicationDate":"2018-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865718802931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36690071","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}