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Genomic imprinting is an epigenetic phenomenon that differentiates maternal and paternal copies of genes in the genome and causes monoallelic expression depending on parental origin. Imprinting is an evolutionary puzzle, as it bears the costs of diploidization without its advantages, namely, protection from recessive mutations. The aim of this review is to answer the question of why genomic imprinting arose and became fixed in the evolution of angiosperms, insects, marsupials, and placental mammals. [ABSTRACT FROM AUTHOR]

Currently, the question of epigenetic mechanisms of gene regulation in the context of cardiovascular diseases is of considerable interest. Here, DNA methylation profiles of vascular tissues of atherosclerotic patients have been analyzed for the first time using the Infinium Human Methylation27 BeadChip microarray (Illumina, United States). As the result, within 286 genes, 314 CpG sites that varied significantly in the level of DNA methylation between the tissue samples of carotid (in the area of atherosclerotic plaques and nearby macroscopically intact tissues of the vascular wall) and mammary arteries, as well as saphenous veins have been identified. The most pronounced differences in the methylation level was registered for CpG sites of homeobox genes HOXA2 and HOXD4, as well as the imprinted MEST gene. In particular, these genes were found to be hypomethylated in the carotid atherosclerotic plaques compared to their methylation patterns in intact tissues of internal mammary arteries and saphenous veins. [ABSTRACT FROM AUTHOR]

For the first time, the epigenetic status of breast benign proliferative processes, malignant breast tumors, and metastases to regional lymph nodes has been studied using the GoldenGate Cancer Panel I DNA methylation microarray (Illumina, United States). The functional groups of differentially methylated genes were identified in each set of samples. The aberrant methylation of genes that regulate cell proliferation and mobility was found in the samples of benign proliferative breast processes. The aberrant methylation of genes responsible for cell differentiation and proliferation, as well as protein phosphorylation and cell mobility, was observed in the samples of malignant breast tumors. The differential methylation of the genes that regulate cell adhesion, the formation of anatomical structures, angiogenesis, immune response, signal transduction, and protein phosphorylation were found in samples with metastases to regional lymph nodes compared to the unaltered breast epithelium. It was found that tissues that range from benign proliferative processes and metastases to regional lymph nodes were generally characterized by a relatively lower level of epigenetic variability compared to the tissues of the primary tumor. [ABSTRACT FROM AUTHOR]

Mutation theory of atherogenesis proved by 'loss of heterozygosity' and microsatellite instability in the area of atherosclerotic plaques is complemented by data on epigenetic variability of genetic loci involved in the pathologic process. However, only recently large-scale analysis of epigenetic modifications in the human genome became possible. For the first time, the quantitative microarray-based methylation profiling of 1505 CpG-sites in 807 genes was performed in atherosclerotic plaques of aorta and carotid artery from humans using the GoldenGate Methylation Cancer Panel I (Illumina, United States). One hundred and three (7%) CpG-sites in 90 (11%) genes were differentially methylated between tissue samples. The most pronounced differences in DNA methylation levels were registered for a site located in CpG-island of the imprinted gene H19. By comparing 90 genes that were differentially methylated between tissue samples in our study, 10 genes ( ICAM1, GSTM1, IGFBP1, POMC, APOA1, IL1RN, INS, LTA, MMP3, THBS2) were overlapped with data in the Human Genome Epidemiology Network (HuGENet), in which they were identified as candidates for cardiovascular disease continuum. [ABSTRACT FROM AUTHOR]

Early stages of human embryonic development are characterized by the spatiotemporal coincidence of events of total epigenetic genome reprogramming and elevated level of mosaic forms of numerical chromosome abnormalities. It is possible that the abnormal reprogramming of various regions of the genome can lead to violations of local epigenetic chromatin organization and gene expression, which affect the correct chromosome segregation during mitosis. In this study, a comparative analysis of the methylation index of LINE-1 retrotransposon, which largely reflects the methylation profile of the genome, is performed in placental tissues of spontaneous abortions with complete and mosaic forms of aneuploidy and with a normal karyotype, as well as in the control group of induced abortions of the first trimester of pregnancy. It was shown that extraembryonic mesoderm and chorionic cytotrophoblast of spontaneous abortions with chromosomal mosaicism are characterized by the highest index of LINE-1 methylation among all studied groups. At the same time, the excessive hypomethylation of transposable genetic element was registered in spontaneous abortions with normal karyotype. We hypothesize that violations of parental genome demethylation during epigenetic reprogramming at preimplantation stages of development may be associated with an increased frequency of mitotic errors in chromosome segregation, which leads to the formation of a mosaic karyotype. [ABSTRACT FROM AUTHOR]

The methylation profiles of the placental tissues of human embryos with normal karyotype and trisomy 16 were compared using an Infinium HumanMethylation27 BeadChip array (Illumina, United States). Numerous differences between the extraembryonic tissues with diploid and aneuploid karyotypes were observed. The extraembryonic mesoderm of embryos with trisomy 16 appeared to be less methylated than the diploid tissue, whereas the cytotrophoblast of aneuploid embryos was hypermethylated. The presence of the supernumerary chromosome was shown to influence the epigenetic profile of the genome by changing the level of methylation of CpG sites of all chromosomes. However, the largest number of differentially methylated loci was found on chromosome 16. Furthermore, more often, the epimutations were tissuespecific. In both tissues, the hypomethylated genes belong to the groups of genes responsible for different metabolic processes, whereas the hypermethylated genes control the processes of development, cell adhesion, immune response, and response to stimulus. [ABSTRACT FROM AUTHOR]

Genomic imprinting is one of the key epigenetic phenomena involved in embryonic development of eutherians and humans. Molecular mechanisms of imprinting disturbances in the pathology of prenatal and postnatal onthogenesis are to a great extent related to methylation abnormalities of the imprinted genes. Over recent years, data are accumulating on multiple abnormalities of methylation simultaneously in several imprinted loci in the development of various pathologies that raises the issue of deciphering the structural and functional organization of imprintome and the interaction of imprinted genes. The present work analyzes DNA methylation of 51 imprinted genes in the placental tissues of human spontaneous abortions. We revealed multiple epimutations in from four to 12 imprinted genes in every embryo. Most of the epimutations (78%) were of a postzygotic origin. It has been established for the first time that the total incidence of methylation disturbance in maternal and paternal alleles of the imprinted genes leading to embryo development suppression is significantly higher than the incidence of epimutations, which stimulate embryogenesis. This fact supports at the epigenetic level the hypothesis of parent-offspring conflict that describes the occurrence of a monoallelic expression of imprinted genes in mammalian evolution. [ABSTRACT FROM AUTHOR]

For the first time, DNA methylation patterns in the human cytotrophoblast and the extraembryonic mesoderm were determined using a genome-wide Infinium HumanMethylation27 BeadChip Array (Illumina, United States). These tissues are derivatives of the trophectoderm and the inner cell mass of the blastocyst and have substantial differences in the dynamics of epigenetic genome reprogramming during early stages of differentiation. It was shown that the genome of the extraembryonic mesoderm cells was more methylated than that of the cytotrophoblast, similarly to the findings in other mammalian species. There were differences in the methylation patterns of single CpG dinucleotides and dinucleotides located within promoter CpG islands: in both tissues most single CpG dinucleotides were methylated, promoters CpG island sites were not. A comparative analysis revealed 202 differentially methylated genes in the extraembryonic mesoderm and 40 such genes in the cytotrophoblast. These genes are responsible for a number of diverse biological processes. However, in the extraembryonic mesoderm, a majority of genes identified were responsible for DNA binding and transcriptional factor activity, whereas those identified in the cytotrophoblast were responsible for transport and protein and cytokine secretion. [ABSTRACT FROM AUTHOR]

Epigenetic mechanisms of cell cycle regulation providing for maintenance of genome stability and precise transmission of hereditary information to the daughter cells attract considerable interest. Up-to-date molecular technologies allow the genome-wide methylation pattern to be determined in a single experiment. In this work, we pioneered in determining the epigenetic status of the placental tissues of the human embryos with mosaic karyotype using a genome-wide Illumina Infinium HumanMethylation27 BeadChip array (Illumina, United States), comprising 27578 CpG dinucleotides contained in 14475 genes. The groups of genes associated with the cell cycle and its regulation that contain differentially methylated CpG sites in their promoter regions have been determined. It was demonstrated that the methylation level most frequently changed in oncogenes ( ARHGEF1 and FGF5), tumor suppressors ( APC2, BRACA2, DCC, GRLF1, RB1, TP73, TSPYL2, and VHL), and the genes involved in the regulation of chromosome segregation ( CNTROB, GMNN, PROCR, and TACC1). [ABSTRACT FROM AUTHOR]