Epitranscriptomics in Hematopoiesis and Hematologic Malignancies.Blood Cancer Discovery 22 Jun 2020, .
Since the 1960s, a large number of chemical modifications have been identified in RNA molecules, establishing the RNA epigenetics field named “epitranscriptomics.” These chemical marks participate in several RNA metabolic processes; however, the biological relevance of many of these modifications and the many enzymes involved in their function is not completely understood. Emerging knowledge of the epitranscriptome (pseudouridine, N6-methyladenosine, and A-to-I editing) in hematopoiesis and hematologic malignancies reveals the requirement of these modifications in normal development and their alteration in disorders, leading to the development of new molecules and strategies to target the epitranscriptome as a novel therapeutic approach. RNA modifications are required for the correct development of hematopoietic cells, and their alteration can promote the development of malignancies or the transition from a low-grade to an aggressive disease. While we are expanding our understanding of the epitranscriptome of normal and malignant hematopoiesis, the number of potential new therapeutic interventions is rising.
The DNA methylation landscape of hematological malignancies: an update.Mol Oncol 11 Jun 2020, . Epub 11 Jun 2020
The rapid advances in high-throughput sequencing technologies have made it more evident that epigenetic modifications orchestrate a plethora of complex biological processes. During the last decade, we have gained significant knowledge about a wide range of epigenetic changes that crucially contribute to some of the most aggressive forms of leukemia, lymphoma and myelodysplastic syndromes. DNA methylation is a key epigenetic player in the abnormal initiation, development and progression of these malignancies, often acting in synergy with other epigenetic alterations. It also contributes to the acquisition of drug resistance. In this review, we summarize the role of DNA methylation in hematological malignancies described in the current literature. We discuss in detail the dual role of DNA methylation in normal and aberrant hematopoiesis, as well as the involvement of this type of epigenetic change in other aspects of the disease. Finally, we present a comprehensive overview of the main clinical implications, including a discussion of the therapeutic strategies that regulate or reverse aberrant DNA methylation patterns in hematological malignancies, including their combination with (chemo-) immunotherapy.Més informació
CTCF is dispensable for immune cell transdifferentiation but facilitates an acute inflammatory response.Nat. Genet. 8 Jun 2020, . Epub 8 Jun 2020
Three-dimensional organization of the genome is important for transcriptional regulationMés informació
Mechanisms of epigenetic inheritance of variable traits through the germline.Reproduction Jun 2020, 159 (6) R251-R263. Epub 22 Abr 2020
During the past half century, evidence for inheritance of variable traits has accumulated from experiments in plants and animals and epidemiological studies in humans. Here, we summarize some of the reported cases of epigenetic inheritance and the proposed mechanisms involved in the transmission of non-genetic information between generations in plants, nematodes, flies and mammals. It has long been accepted that information is epigenetically inherited in plants. Although many questions regarding the underlying mechanisms remain to be answered, it is now evident that epigenetic mechanisms are also responsible for the transmission of phenotypes in animals. We highlight similarities and differences between models and species.Més informació