L-Ascorbic Acid in the Epigenetic Regulation of Cancer Development and Stem Cell Reprogramming.

Recent studies have significantly expanded our understanding of the mechanisms of L-ascorbic acid (ASC, vitamin C) action, leading to the emergence of several hypotheses that validate the possibility of using ASC in clinical practice. ASC may be considered an epigenetic drug capable of reducing aberrant DNA and histone hypermethylation, which could be helpful in the treatment of some cancers and neurodegenerative diseases. The clinical potency of ASC is also associated with regenerative medicine; in particular with the production of iPSCs. The effect of ASC on somatic cell reprogramming is most convincingly explained by a combined enhancement of the activity of the enzymes involved in the active demethylation of DNA and histones. This review describes how ASC can affect the epigenetic status of a cell and how it can be used in anticancer therapy and stem cell reprogramming.

Genetic and Epigenetic Mechanisms of ß-Globin Gene Switching.

Vertebrates have multiple forms of hemoglobin that differ in the composition of their polypeptide chains. During ontogenesis, the composition of these subunits changes. Genes encoding different α- and ß-polypeptide chains are located in two multigene clusters on different chromosomes. Each cluster contains several genes that are expressed at different stages of ontogenesis. The phenomenon of stage-specific transcription of globin genes is referred to as globin gene switching. Mechanisms of expression switching, stage-specific activation, and repression of transcription of α- and ß-globin genes are of interest from both theoretical and practical points of view. Alteration of balanced expression of globin genes, which usually occurs due to damage to adult ß-globin genes, leads to development of severe diseases - hemoglobinopathies. In most cases, reactivation of the fetal hemoglobin gene in patients with ß-thalassemia and sickle cell disease can reduce negative consequences of irreversible alterations of expression of the ß-globin genes. This review focuses on the current state of research on genetic and epigenetic mechanisms underlying stage-specific switching of ß-globin genes.

Effect of Environmental Factors on Nuclear Organization and Transformation of Human B Lymphocytes.

Chromosomal translocations have long been known for their association with malignant transformation, particularly in hematopoietic disorders such as B-cell lymphomas. In addition to the physiological process of maturation, which creates double strand breaks in immunoglobulin gene loci, environmental factors including the Epstein-Barr and human immunodeficiency viruses, malaria-causing parasites (Plasmodium falciparum), and plant components (Euphorbia tirucalli latex) can trigger a reorganization of the nuclear architecture and DNA damage that together will facilitate the occurrence of deleterious chromosomal rearrangements.

[Main regulatory element (MRE) of the Danio rerio α/ß-globin gene domain exerts enhancer activity toward the promoters of the embryonic-larval and adult globin genes].

In warm-blooded vertebrates, the α- and ß-globin genes are organized in domains of different types and are regulated in different fashion. In cold-blooded vertebrates and, in particular, the tropical fish Danio rerio, the α- and ß-globin genes form two gene clusters. A major D. rerio globin gene cluster is in chromosome 3 and includes the α- and ß-globin genes of embryonic-larval and adult types. The region upstream of the cluster contains c16orf35, harbors the main regulatory element (MRE) of the α-globin gene domain in warm-blooded vertebrates. In this study, transient transfection of erythroid cells with genetic constructs containing a reporter gene under the control of potential regulatory elements of the domain was performed to characterize the promoters of the embryonic-larval and adult α- and ß-globin genes of the major cluster. Also, in the 5th intron of c16orf35 in Danio reriowas detected a functional analog of the warm-blooded vertebrate MRE. This enhancer stimulated activity of the promoters of both adult and embryonic-larval α- and ß-globin genes.