scholarly journals Urinary expression of genes involved in DNA methylation and histone modification for diagnosis of bladder cancer in patients with asymptomatic microscopic haematuria

2019 ◽  
Author(s):  
Ilaria Lucca ◽  
Sebastian Hofbauer ◽  
Andrea Haitel ◽  
Martin Susani ◽  
Shahrokh Shariat ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Histone Modification ◽  
Microscopic Haematuria ◽  
Expression Of Genes

Epigenetic modifications in acute lymphoblastic leukemia: From cellular mechanisms to therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Ezzatollah Fathi ◽  
Raheleh Farahzadi ◽  
Soheila Montazersaheb ◽  
Yasin Bagheri
Keyword(s):  
Dna Methylation ◽  
Acute Lymphoblastic Leukemia ◽  
Histone Modification ◽  
Epigenetic Modification ◽  
Lymphoblastic Leukemia ◽  
Underlying Mechanism ◽  
Methylation Pattern ◽  
Epigenetic Alterations ◽  
Cellular Mechanisms ◽  
Novel Treatments

Background:: Epigenetic modification pattern is considered as a characteristic feature in blood malignancies. Modifications in the DNA methylation modulators are recurrent in lymphoma and leukemia, so that, the distinct methylation pattern defines different types of leukemia. Generally, the role of epigenetics is less understood and most investigations are focused on genetic abnormalities and cytogenic studies to develop novel treatments for patients with hematologic disorders. Recently, understanding the underlying mechanism of acute lymphoblastic leukemia (ALL), especially epigenetic altera-tions as a driving force in the development of ALL opens a new era of investigation for developing promising strategy, be-yond available conventional therapy. Objective:: This review will focus on a better understanding of the epigenetic mechanisms in cancer development and pro-gression, with an emphasis on epigenetic alterations in ALL including, DNA methylation, histone modification, and mi-croRNA alterations. Other topics that will be discussed include the use of epigenetic alterations as a promising therapeutic target in order to develop novel well-suited approaches against ALL. Conclusion:: According to the literature review, leukemogenesis of ALL is extensively influenced by epigenetic modifica-tions, particularly DNA hyper-methylation, histone modification, and miRNA alteration.

scholarly journals Natural Antisense Transcript PEBP1P3 Regulates the RNA Expression, DNA Methylation and Histone Modification of CD45 Gene

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 759
Author(s):  
Zhongjing Su ◽  
Guangyu Liu ◽  
Bin Zhang ◽  
Ze Lin ◽  
Dongyang Huang
Keyword(s):  
Dna Methylation ◽  
Alternative Splicing ◽  
Histone Modification ◽  
Antisense Rna ◽  
Noncoding Rna ◽  
Antisense Transcript ◽  
Natural Antisense Transcript ◽  
Regulation Of Expression ◽  
Splicing Isoforms ◽  
Intron 2

The leukocyte common antigen CD45 is a transmembrane phosphatase expressed on all nucleated hemopoietic cells, and the expression levels of its splicing isoforms are closely related to the development and function of lymphocytes. PEBP1P3 is a natural antisense transcript from the opposite strand of CD45 intron 2 and is predicted to be a noncoding RNA. The genotype-tissue expression and quantitative PCR data suggested that PEBP1P3 might be involved in the regulation of expression of CD45 splicing isoforms. To explore the regulatory mechanism of PEBP1P3 in CD45 expression, DNA methylation and histone modification were detected by bisulfate sequencing PCR and chromatin immunoprecipitation assays, respectively. The results showed that after the antisense RNA PEBP1P3 was knocked down by RNA interference, the DNA methylation of CD45 intron 2 was decreased and histone H3K9 and H3K36 trimethylation at the alternative splicing exons of CD45 DNA was increased. Knockdown of PEBP1P3 also increased the binding levels of chromatin conformation organizer CTCF at intron 2 and the alternative splicing exons of CD45. The present results indicate that the natural antisense RNA PEBP1P3 regulated the alternative splicing of CD45 RNA, and that might be correlated with the regulation of histone modification and DNA methylation.

DNA methyltransferase inhibitors modulate histone methylation: epigenetic crosstalk between H3K4me3 and DNA methylation during sperm differentiation

Zygote ◽  
2021 ◽  
pp. 1-6
Author(s):  
Liliana Burlibaşa ◽  
Alina-Teodora Nicu ◽  
Carmen Domnariu
Keyword(s):  
Dna Methylation ◽  
Histone Methylation ◽  
Dna Methyltransferase ◽  
Integrated Approach ◽  
Regulatory Mechanisms ◽  
Temporal Expression ◽  
Dna Methyltransferase Inhibitors ◽  
Expression Of Genes ◽  
Species Survival ◽  
Advanced Stages

Summary The process of cytodifferentiation in spermatogenesis is governed by a unique genetic and molecular programme. In this context, accurate ‘tuning’ of the regulatory mechanisms involved in germ cells differentiation is required, as any error could have dramatic consequences on species survival and maintenance. To study the processes that govern the spatial–temporal expression of genes, as well as analyse transmission of epigenetic information to descendants, an integrated approach of genetics, biochemistry and cytology data is necessary. As information in the literature on interplay between DNA methylation and histone H3 lysine 4 trimethylation (H3K4me3) in the advanced stages of murine spermatogenesis is still scarce, we investigated the effect of a DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine, at the cytological level using immunocytochemistry methodology. Our results revealed a particular distribution of H3K4me3 during sperm cell differentiation and highlighted an important role for regulation of DNA methylation in controlling histone methylation and chromatin remodelling during spermatogenesis.

scholarly journals A urine-based DNA methylation assay to facilitate early detection and risk stratification of bladder cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Weimei Ruan ◽  
Xu Chen ◽  
Ming Huang ◽  
Hong Wang ◽  
Jiaxin Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Risk Stratification ◽  
Early Stage ◽  
Operative Risk ◽  
Low Grade ◽  
Single Center ◽  
Detection Model ◽  
Methylation Assay ◽  
Muscle Invasive

Abstract Background Current non-invasive tests have limited sensitivities and lack capabilities of pre-operative risk stratification for bladder cancer (BC) diagnosis. We aimed to develop and validate a urine-based DNA methylation assay as a clinically feasible test for improving BC detection and enabling pre-operative risk stratifications. Methods A urine-based DNA methylation assay was developed and validated by retrospective single-center studies in patients of suspected BC in Cohort 1 (n = 192) and Cohort 2 (n = 98), respectively. In addition, a prospective single-center study in hematuria patient group (Cohort 3, n = 174) was used as a second validation of the model. Results The assay with a dual-marker detection model showed 88.1% and 91.2% sensitivities, 89.7% and 85.7% specificities in validation Cohort 2 (patients of suspected BC) and Cohort 3 (patients of hematuria), respectively. Furthermore, this assay showed improved sensitivities over cytology and FISH on detecting low-grade tumor (66.7–77.8% vs. 0.0–22.2%, 0.0–22.2%), Ta tumor (83.3% vs. 22.2–41.2%, 44.4–52.9%) and non-muscle invasive BC (NMIBC) (80.0–89.7% vs. 51.5–52.0%, 59.4–72.0%) in both cohorts. The assay also had higher accuracies (88.9–95.8%) in diagnosing cases with concurrent genitourinary disorders as compared to cytology (55.6–70.8%) and FISH (72.2–77.8%). Meanwhile, the assay with a five-marker stratification model identified high-risk NMIBC and muscle invasive BC with 90.5% sensitivity and 86.8% specificity in Cohort 2. Conclusions The urine-based DNA methylation assay represents a highly sensitive and specific approach for BC early-stage detection and risk stratification. It has a potential to be used as a routine test to improve diagnosis and prognosis of BC in clinic.

scholarly journals Association of expression of epigenetic molecular factors with DNA methylation and sensitivity to chemotherapeutic agents in cancer cell lines

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Suleyman Vural ◽  
Alida Palmisano ◽  
William C. Reinhold ◽  
Yves Pommier ◽  
Beverly A. Teicher ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Chemotherapeutic Agents ◽  
Epigenetic Factors ◽  
Expression Of Genes ◽  
Genes Encoding

Abstract Background Altered DNA methylation patterns play important roles in cancer development and progression. We examined whether expression levels of genes directly or indirectly involved in DNA methylation and demethylation may be associated with response of cancer cell lines to chemotherapy treatment with a variety of antitumor agents. Results We analyzed 72 genes encoding epigenetic factors directly or indirectly involved in DNA methylation and demethylation processes. We examined association of their pretreatment expression levels with methylation beta-values of individual DNA methylation probes, DNA methylation averaged within gene regions, and average epigenome-wide methylation levels. We analyzed data from 645 cancer cell lines and 23 cancer types from the Cancer Cell Line Encyclopedia and Genomics of Drug Sensitivity in Cancer datasets. We observed numerous correlations between expression of genes encoding epigenetic factors and response to chemotherapeutic agents. Expression of genes encoding a variety of epigenetic factors, including KDM2B, DNMT1, EHMT2, SETDB1, EZH2, APOBEC3G, and other genes, was correlated with response to multiple agents. DNA methylation of numerous target probes and gene regions was associated with expression of multiple genes encoding epigenetic factors, underscoring complex regulation of epigenome methylation by multiple intersecting molecular pathways. The genes whose expression was associated with methylation of multiple epigenome targets encode DNA methyltransferases, TET DNA methylcytosine dioxygenases, the methylated DNA-binding protein ZBTB38, KDM2B, SETDB1, and other molecular factors which are involved in diverse epigenetic processes affecting DNA methylation. While baseline DNA methylation of numerous epigenome targets was correlated with cell line response to antitumor agents, the complex relationships between the overlapping effects of each epigenetic factor on methylation of specific targets and the importance of such influences in tumor response to individual agents require further investigation. Conclusions Expression of multiple genes encoding epigenetic factors is associated with drug response and with DNA methylation of numerous epigenome targets that may affect response to therapeutic agents. Our findings suggest complex and interconnected pathways regulating DNA methylation in the epigenome, which may both directly and indirectly affect response to chemotherapy.

scholarly journals Global impacts of chromosomal imbalance on gene expression in Arabidopsis and other taxa

2018 ◽  
Vol 115 (48) ◽  
pp. E11321-E11330 ◽  
Author(s):  
Jie Hou ◽  
Xiaowen Shi ◽  
Chen Chen ◽  
Md. Soliman Islam ◽  
Adam F. Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factors ◽  
Leaf Tissue ◽  
Global Gene Expression ◽  
Published Data ◽  
Chromosomal Imbalance ◽  
Regulatory Processes ◽  
Expression Of Genes ◽  
Global Impacts

Changes in dosage of part of the genome (aneuploidy) have long been known to produce much more severe phenotypic consequences than changes in the number of whole genomes (ploidy). To examine the basis of these differences, global gene expression in mature leaf tissue for all five trisomies and in diploids, triploids, and tetraploids of Arabidopsis thaliana was studied. The trisomies displayed a greater spread of expression modulation than the ploidy series. In general, expression of genes on the varied chromosome ranged from compensation to dosage effect, whereas genes from the remainder of the genome ranged from no effect to reduced expression approaching the inverse level of chromosomal imbalance (2/3). Genome-wide DNA methylation was examined in each genotype and found to shift most prominently with trisomy 4 but otherwise exhibited little change, indicating that genetic imbalance is generally mechanistically unrelated to DNA methylation. Independent analysis of gene functional classes demonstrated that ribosomal, proteasomal, and gene body methylated genes were less modulated compared with all classes of genes, whereas transcription factors, signal transduction components, and organelle-targeted protein genes were more tightly inversely affected. Comparing transcription factors and their targets in the trisomies and in expression networks revealed considerable discordance, illustrating that altered regulatory stoichiometry is a major contributor to genetic imbalance. Reanalysis of published data on gene expression in disomic yeast and trisomic mouse cells detected similar stoichiometric effects across broad phylogenetic taxa, and indicated that these effects reflect normal gene regulatory processes.

scholarly journals Identification of Novel Gene Targets and Putative Regulators of Arsenic-Associated DNA Methylation in Human Urothelial Cells and Bladder Cancer

2015 ◽  
Vol 28 (6) ◽  
pp. 1144-1155 ◽  
Author(s):  
Julia E. Rager ◽  
Sloane K. Tilley ◽  
Samantha E. Tulenko ◽  
Lisa Smeester ◽  
Paul D. Ray ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Urothelial Cells ◽  
Novel Gene
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