Epigenetics Insights最新文献

{"title":"Evidence of an Epigenetics System in Archaea","authors":"P. Blum, Sophie Payne","doi":"10.1177/2516865719865280","DOIUrl":"https://doi.org/10.1177/2516865719865280","url":null,"abstract":"Changes in the phenotype of a cell or organism that are heritable but do not involve changes in DNA sequence are referred to as epigenetic. They occur primarily through the gain or loss of chemical modification of chromatin protein or DNA. Epigenetics is therefore a non-Mendelian process. The study of epigenetics in eukaryotes is expanding with advances in knowledge about the relationship between mechanism and phenotype and as a requirement for multicellularity and cancer. However, life also includes other groups or domains, notably the bacteria and archaea. The occurrence of epigenetics in these deep lineages is an emerging topic accompanied by controversy. In these non-eukaryotic organisms, epigenetics is critically important because it stimulates new evolutionary theory and refines perspective about biological action.","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719865280","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48184763","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}

{"title":"Stop-and-Go: Dynamics of Nucleolar Transcription During the Cell Cycle.","authors":"Aishwarya Iyer-Bierhoff, Ingrid Grummt","doi":"10.1177/2516865719849090","DOIUrl":"https://doi.org/10.1177/2516865719849090","url":null,"abstract":"Entry into mitosis correlates with nucleolar disassembly and shutdown of ribosomal RNA (rRNA) gene (rDNA) transcription. In telophase, nucleoli reform and transcription is reactivated. The molecular mechanisms underlying the dynamics of nucleolar transcription during the cell cycle are manifold. Although mitotic inactivation of the RNA polymerase I (Pol I) transcription machinery by posttranslational modifications has been extensively studied, little is known about the structure of rDNA chromatin during progression through mitosis. Methylation of histone H2A at glutamine 104 (H2AQ104me), a dedicated nucleolar histone modification, is lost in prometaphase, leading to chromatin compaction, which enforces mitotic repression of rRNA genes. At telophase, restoration of H2AQ104me is required for the activation of transcription. H2AQ104 methylation and chromatin dynamics are regulated by fibrillarin (FBL) and the NAD+-dependent nucleolar deacetylase sirtuin 7 (SIRT7). Deacetylation of FBL is required for the methylation of H2AQ104 and high levels of rDNA transcription during interphase. At the entry into mitosis, nucleoli disassemble and FBL is hyperacetylated, leading to loss of H2AQ104me, chromatin compaction, and shutdown of Pol I transcription. These results reveal that reversible acetylation of FBL regulates methylation of nucleolar H2AQ104, thereby reinforcing oscillation of Pol I transcription during the cell cycle.","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2019-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719849090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37337444","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":"Enhancer RNAs: Insights Into Their Biological Role.","authors":"Josué Cortés-Fernández de Lara,&nbsp;Rodrigo G Arzate-Mejía,&nbsp;Félix Recillas-Targa","doi":"10.1177/2516865719846093","DOIUrl":"10.1177/2516865719846093","url":null,"abstract":"<p><p>Enhancers play a central role in the transcriptional regulation of metazoans. Almost a decade ago, the discovery of their pervasive transcription into noncoding RNAs, termed enhancer RNAs (eRNAs), opened a whole new field of study. The presence of eRNAs correlates with enhancer activity; however, whether they act as functional molecules remains controversial. Here we review direct experimental evidence supporting a functional role of eRNAs in transcription and provide a general pipeline that could help in the design of experimental approaches to investigate the function of eRNAs. We propose that induction of transcriptional activity at enhancers promotes an increase in its activity by an RNA-mediated titration of regulatory proteins that can impact different processes like chromatin accessibility or chromatin looping. In a few cases, transcripts originating from enhancers have acquired specific molecular functions to regulate gene expression. We speculate that these transcripts are either nonannotated long noncoding RNAs (lncRNAs) or are evolving toward functional lncRNAs. Further work will be needed to comprehend better the biological activity of these transcripts.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2019-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719846093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36992217","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":"Transgenerational Epigenetic Inheritance Is Revealed as a Multi-step Process by Studies of the SET-Domain Proteins SET-25 and SET-32.","authors":"Rachel M Woodhouse,&nbsp;Alyson Ashe","doi":"10.1177/2516865719844214","DOIUrl":"https://doi.org/10.1177/2516865719844214","url":null,"abstract":"<p><p>It is now clear that heredity is not determined purely by Mendelian genetic inheritance; sometimes, epigenetic signals can be passed from parent to progeny for multiple generations. This phenomenon is termed transgenerational epigenetic inheritance (TEI), and examples have now been observed in multiple organisms including plants, flies, mice, and nematodes. Here we discuss the recent findings that TEI is a multi-step process and that the putative chromatin modifiers SET-25 and SET-32 are important in the establishment but not maintenance of silencing.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2019-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719844214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37182322","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":"Succinate Dehydrogenase-Deficient Gastrointestinal Stromal Tumors: Small Steps Toward Personalized Medicine?","authors":"Gloria Ravegnini,&nbsp;Riccardo Ricci","doi":"10.1177/2516865719842534","DOIUrl":"https://doi.org/10.1177/2516865719842534","url":null,"abstract":"<p><p>Various molecular triggers define heterogeneous subsets of gastrointestinal stromal tumors (GISTs), differing in clinical behavior and drug sensitivity. <i>KIT/PDGFRA</i>-wild-type GISTs, including those succinate dehydrogenase (SDH)-deficient, are overall unresponsive to the tyrosine kinase inhibitors commonly used, fostering the development of specific alternative therapeutic strategies. Epigenetic inactivation of O⁶-methylguanine-DNA methyltransferase (MGMT) through promoter methylation leads to effectiveness of alkylating agents in several human cancers. SDH-deficient GISTs typically feature widespread DNA methylation. However, the actual occurrence of <i>MGMT</i> methylation in these tumors, potentially predisposing them to respond to alkylating drugs, has not been investigated so far. Here we discuss the recent findings concerning the occurrence of <i>MGMT</i> methylation in different GIST subgroups, including SDH-deficient ones, as a premise for a possible reappraisal of alkylating agents specifically targeting these small, otherwise overall chemorefractory, GIST subgroups.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2019-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719842534","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37182321","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":"Thymoquinone-Induced Reactivation of Tumor Suppressor Genes in Cancer Cells Involves Epigenetic Mechanisms.","authors":"Shahad A Qadi,&nbsp;Mohammed A Hassan,&nbsp;Ryan A Sheikh,&nbsp;Othman As Baothman,&nbsp;Mazin A Zamzami,&nbsp;Hani Choudhry,&nbsp;Abdulrahman Labeed Al-Malki,&nbsp;Ashwag Albukhari,&nbsp;Mahmoud Alhosin","doi":"10.1177/2516865719839011","DOIUrl":"https://doi.org/10.1177/2516865719839011","url":null,"abstract":"<p><p>The epigenetic silencing of tumor suppressor genes (TSGs) is a common finding in several solid and hematological tumors involving various epigenetic readers and writers leading to enhanced cell proliferation and defective apoptosis. Thymoquinone (TQ), the major biologically active compound of black seed oil, has demonstrated anticancer activities in various tumors by targeting several pathways. However, its effects on the epigenetic code of cancer cells are largely unknown. In the present study, we performed RNA sequencing to investigate the anticancer mechanisms of TQ-treated T-cell acute lymphoblastic leukemia cell line (Jurkat cells) and examined gene expression using different tools. We found that many key epigenetic players, including ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 (<i>UHRF1), DNMT1,3A,3B, G9A, HDAC1,4,9, KDM1B</i>, and <i>KMT2A,B,C,D,E</i>, were downregulated in TQ-treated Jurkat cells. Interestingly, several TSGs, such as <i>DLC1, PPARG, ST7, FOXO6, TET2, CYP1B1, SALL4</i>, and <i>DDIT3</i>, known to be epigenetically silenced in various tumors, including acute leukemia, were upregulated, along with the upregulation of several downstream pro-apoptotic genes, such as <i>RASL11B, RASD1, GNG3, BAD</i>, and <i>BIK</i>. Data obtained from RNA sequencing were confirmed using quantitative reverse transcription polymerase chain reaction (RT-qPCR) in Jurkat cells, as well as in a human breast cancer cell line (MDA-MB-468 cells). We found that the decrease in cell proliferation and in the expression of <i>UHRF1, DNMT1, G9a</i>, and <i>HDAC1</i> genes in both cancer cell (Jurkat cells and MDA-MB-468 cells) lines depends on the TQ dose. Our results indicate that the use of TQ as an epigenetic drug represents a promising strategy for epigenetic therapy for both solid and blood tumors by targeting both DNA methylation and histone post-translational modifications.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2019-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719839011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37391148","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":"Epigenetic Classifiers for Precision Diagnosis of Brain Tumors.","authors":"Javier Ij Orozco,&nbsp;Ayla O Manughian-Peter,&nbsp;Matthew P Salomon,&nbsp;Diego M Marzese","doi":"10.1177/2516865719840284","DOIUrl":"https://doi.org/10.1177/2516865719840284","url":null,"abstract":"<p><p>DNA methylation profiling has proven to be a powerful analytical tool, which can accurately identify the tissue of origin of a wide range of benign and malignant neoplasms. Using microarray-based profiling and supervised machine learning algorithms, we and other groups have recently unraveled DNA methylation signatures capable of aiding the histomolecular diagnosis of different tumor types. We have explored the methylomes of metastatic brain tumors from patients with lung cancer, breast cancer, and cutaneous melanoma and primary brain neoplasms to build epigenetic classifiers. Our brain metastasis methylation (BrainMETH) classifier has the ability to determine the type of brain tumor, the origin of the metastases, and the clinical-therapeutic subtype for patients with breast cancer brain metastases. To facilitate the translation of these epigenetic classifiers into clinical practice, we selected and validated the most informative genomic regions utilizing quantitative methylation-specific polymerase chain reaction (qMSP). We believe that the refinement, expansion, integration, and clinical validation of BrainMETH and other recently developed epigenetic classifiers will significantly contribute to the development of more comprehensive and accurate systems for the personalized management of patients with brain metastases.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2019-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719840284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37137079","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":"Genomic Balance and Speciation.","authors":"James A Birchler,&nbsp;Reiner A Veitia","doi":"10.1177/2516865719840291","DOIUrl":"https://doi.org/10.1177/2516865719840291","url":null,"abstract":"<p><p>The role of genomic balance in accumulating species hybrid incompatibilities is discussed. Aneuploidy has been shown to produce more global modulations than polyploidy with the responsible genes being transcription factors and signaling components involved in molecular complexes, illustrating a stoichiometric component to gene expression. Genomic imbalance is usually detrimental to the organism and in many cases results in lethality. Here, it is proposed that once gene flow is prevented between or within populations by various speciation initiating processes, the stoichiometric relationship of members of macromolecular complexes can change via compensatory drift with the eventual result of newly established functional balances. However, when these new relationships are brought together in interspecific hybrids, detrimental consequences will occur. We suggest that these detrimental interactions contribute to hybrid incompatibilities.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2019-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719840291","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37137080","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":"<i>K-RAS</i> Mutant Gene Found in Pancreatic Juice Activated Chromatin From Peri-ampullary Adenocarcinomas.","authors":"Joseph Reza,&nbsp;Alvin Jo Almodovar,&nbsp;Milan Srivastava,&nbsp;Paula P Veldhuis,&nbsp;Swati Patel,&nbsp;Na'im Fanaian,&nbsp;Xiang Zhu,&nbsp;Sally A Litherland,&nbsp;J Pablo Arnoletti","doi":"10.1177/2516865719828348","DOIUrl":"https://doi.org/10.1177/2516865719828348","url":null,"abstract":"<p><p>External pancreatic duct stents inserted after resection of pancreatic head tumors provide unique access to pancreatic juice analysis of genetic and metabolic components that may be associated with peri-ampullary tumor progression. For this pilot study, portal venous blood and pancreatic juice samples were collected from 17 patients who underwent pancreaticoduodenectomy for peri-ampullary tumors. Portal vein circulating tumor cells (CTC) were isolated by high-speed fluorescence-activated cell sorting (FACS) and analyzed by quantitative reverse transcription polymerase chain reaction (RT-PCR) for <i>K-RAS</i> exon 12 mutant gene expression (<i>K-RASmut</i>). DNA, chromatin, and histone acetylated active chromatin were isolated from pancreatic juice samples by chromatin immunoprecipitation (ChIP) and the presence of <i>K-RASmut</i> and other cancer-related gene sequences detected by quantitative polymerase chain reaction (PCR) and ChIP-Seq. Mutated <i>K-RAS</i> gene was detectable in activated chromatin in pancreatic juice secreted after surgical resection of pancreatic, ampullary and bile duct carcinomas and directly correlated with the number of CTC found in the portal venous blood (<i>P</i> = .0453). ChIP and ChIP-Seq detected acetylated chromatin in peri-ampullary cancer patient juice containing candidate chromatin loci, including <i>RET</i> proto-oncogene, not found in similar analysis of pancreatic juice from non-malignant ampullary adenoma. The presence of active tumor cell chromatin in pancreatic juice after surgical removal of the primary tumor suggests that viable cancer cells either remain or re-emerge from the remnant pancreatic duct, providing a potential source for tumor recurrence and cancer relapse. Therefore, epigenetic analysis for active chromatin in pancreatic juice and portal venous blood CTC may be useful for prognostic risk stratification and potential identification of molecular targets in peri-ampullary cancers.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2019-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719828348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37008597","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":"Noncatalytic Function of a JmjC Domain Protein Disrupts Heterochromatin","authors":"Kehan Bao, S. Jia","doi":"10.1177/2516865719862249","DOIUrl":"https://doi.org/10.1177/2516865719862249","url":null,"abstract":"Chromatin-modifying enzymes are frequently overexpressed in cancer cells, and their enzymatic activities play important roles in changing the epigenetic landscape responsible for tumorigenesis. However, many of these proteins also execute noncatalytic functions, which are poorly understood. In fission yeast, overexpression of Epe1, a histone demethylase homolog, causes heterochromatin defects. Interestingly, in our recent work, we discovered that overexpressed Epe1 recruits SAGA, a histone acetyltransferase complex important for transcriptional regulation, to disrupt heterochromatin, independent of its demethylase activity. Our findings suggest that overexpressed chromatin-modifying enzymes can alter the epigenetic landscape through changing their proteomic environments, an area that needs to be further explored in dissecting disease etiology associated with overexpression of chromatin regulators.","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719862249","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49566255","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}