Dynamic changes in transposable element and gene methylation in mulberry (Morus notabilis) in response to Botrytis cinerea

DNA methylation has been proposed to regulate plant stress resistance. However, the dynamic changes in DNA methylation in woody plants and their correlations with pathogenic responses are not fully understood. Here, we present single-base maps of the DNA methylomes of mulberry (Morus notabilis) leaves that were subjected to a mock treatment or inoculation with Botrytis cinerea. Compared with the former, the latter showed decreased mCG and mCHG levels and increased mCHH levels. DNA methylation inhibitors reduced resistance gene methylation levels and enhanced mulberry resistance, suggesting that the hypomethylation of resistance genes affects mulberry resistance to B. cinerea. Virus-induced gene silencing of MnMET1 enhanced the expression of mulberry-resistance genes, thereby increasing the plant’s resistance to B. cinerea. We also found that MITEs play a dominant role in controlling DNA methylation levels. MITEs appear to be the main sources of 24-nt siRNAs that regulate gene expression through the RNA-directed DNA methylation pathway.

Predictive biomarkers and potential drug combinations of epi-drugs in cancer therapy

Epigenetics studies heritable genomic modifications that occur with the participation of epigenetic modifying enzymes but without alterations of the nucleotide structure. Small-molecule inhibitors of these epigenetic modifying enzymes are known as epigenetic drugs (epi-drugs), which can cause programmed death of tumor cells by affecting the cell cycle, angiogenesis, proliferation, and migration. Epi-drugs include histone methylation inhibitors, histone demethylation inhibitors, histone deacetylation inhibitors, and DNA methylation inhibitors. Currently, epi-drugs undergo extensive development, research, and application. Although epi-drugs have convincing anti-tumor effects, the patient’s sensitivity to epi-drug application is also a fundamental clinical issue. The development and research of biomarkers for epi-drugs provide a promising direction for screening drug-sensitive patients. Here, we review the predictive biomarkers of 12 epi-drugs as well as the progress of combination therapy with chemotherapeutic drugs or immunotherapy. Further, we discuss the improvement in the development of natural ingredients with low toxicity and low side effects as epi-drugs.

Epigenetic Events in Ovarian Cancer

Epigenetic aberrations are now well established in the development and progression of ovarian cancer, including DNA methylation, histone modifications, and microRNA dysregulation, and their progressive accumulation is correlated with the progression of the stage grade of disease. Epigenetic aberrations are relatively stable, linked to various subtypes of the disease, and present in circulating serum, representing promising diagnostic, prognostic, and pharmacodynamic biomarkers. Unlike DNA mutations and deletions, aberrant gene-repressive epigenetic changes, including DNA methylation inhibitors or histone-modifying enzymes, are theoretically reversible by epigenetic therapies. While no action against solid tumors, including ovarian cancer, has been shown in epigenetic monotherapies, preclinical studies indicate that they may be successful when used in conjunction with one another or with conventional chemotherapy, and combinatorial epigenetic therapy regiments are being investigated in cancer clinical trials. Improved interventions against this debilitating malignancy will provide a greater understanding of epigenetics’ role in ovarian cancer.

A Review of Aberrant DNA Methylation and Epigenetic Agents Targeting DNA Methyltransferases in Endometriosis

Background: Endometriosis (EMS) is a gynecological disease defined by the translocation and growth of endometrial tissue in other tissues or organs outside the uterus. Its clinical manifestations are dysmenorrhea, irregular menstruation, and even infertility. Although EMS is a benign disease, it has the characteristics of malignant tumor and the potential of malignant transformation. Recent studies have found that EMS may involve epigenetic changes and that various epigenetic aberrations, especially aberrant DNA methylation may play an essential role in the pathogenesis of EMS. Previous studies have elucidated the epigenetic regulators of EMS and reported variations in epigenetic patterns of genes known to be associated with abnormal hormonal, immune, and inflammatory states of EMS. With the development of high-throughput sequencing and other biomolecular technologies, we have a better understanding of genome-wide methylation in EMS. Objective: This article will discuss the potentiality of targeting DNA methylation as the therapeutic approach for EMS. Results: This article reviews the role of DNA methylation in the pathophysiology of EMS and provides insight into a novel therapeutic approach for EMS by targeting DNA methylation modifiers. We also review the current progress in using DNA methylation inhibitors in EMS therapy and the potential promise and challenges ahead. Conclusion: Aberrant DNA methylation plays an essential role in the pathogenesis of EMS and epigenetic agents targeting DNA methyltransferases are expected to be the theoretical basis for the new treatment of EMS.