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Results for “epigenetic modification”

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At least 649 records · Page 36Linked to original sources
PubMed2005

No evidence of correlation between the single nucleotide polymorphism of DNMT3B promoter and gastric cancer risk in a Japanese population.

DNA methylation is a major epigenetic modification in humans, and aberrant DNA methylation may play an important role in the development of various cancers through the silencing of some tumor suppressor genes. DNMT3B is required for the establishment and maintenance of genomic methylation patterns. The -149 C/T single nucleotide polymorphism (SNP) in the promoter of DNMT3B has been identified. This SNP influences DNMT3B promoter function, with the T allele having greater activity than the C allele, and is associated with an increased risk of lung cancer. The purpose of our study was to investigate the correlation between the DNMT3B promoter polymorphism and the development and progression of gastric cancer. We analyzed the SNP of the DNMT3B promoter in 152 gastric cancer patients and 247 controls from a Japanese population using PCR-RFLP and sequencing analysis, and also studied the association between the genotypes of DNMT3B and clinicopathological parameters among cases. Allelic difference was not found between gastric cancer patients and control subjects at the target site, -149 bp from the transcriptional start site in the DNMT3B gene promoter. Only the T/T genotype was detected in all gastric cancer patients and control subjects. We concluded that there was no association between SNP of the DNMT3B promoter and gastric cancer risk in a Japanese population.

Case-Control Studies↗
PubMed2005

[How to consider cancer: implications for the risk due to ionizing radiation].

Cancers induced by ionizing radiation have no particular specificity nor genetic remarkable signature, excepting numerous multideletions. They should therefore be studied in the general field of cancer biology in its broad sense. A gap remains between the initial events like the rather well identified genomic damage and the subsequent emerging cellular clone with cancer characteristics. Intermediate steps are generally described as accumulation of mutations and epigenetic modifications leading at one point to the malignant phenotype. However we have no clear nor understandable model on these steps of malignant transformation till now. It is quite possible that specific causes (tobacco, alcohol, radiations, chemical toxics) which produce different initial abnormalities then lead to (or accelerate the entry in) the common and same way as that resulting of accumulations of damage due to ageing. Genomic instability is certainly an important factor involved in the cellular drift leading to malignant transformation. We postulate that only cells having both a high telomerase activity and a low apoptotic activity may become cancerous. The hypothesis is that cancer results from a genome reprogramming of these cells due to an oncogenic mitotic pressure which induces a loss of the differentiation control. We propose to name anti-apoptosis, in contrast to apoptosis which is the programmed death, the ultimate process by which a cell loses its tissue-related properties. The oncogenic activation may propagate to primordial genes of development resulting in emergence of a subnuclear with tumoral activity. Bio-molecular studies of embryonic development and of genome re-programming will probably allow us to better understand the mechanisms of cancer.

Aging↗
PubMed2006

[DNA methylation: an epigenetic mechanism for tumorigenesis].

DNA methylation is a kind of epigenetic modification in human genome. Both hypermethylation of tumor suppressor gene or DNA repair gene and hypomethylation of repetitious DNA are closely related to different kinds of tumors. Loss of imprinting can also cause tumorigenesis. The recent study confirmed that the level of DNA methylation in genome was not only affected by DNA methyltransferase(DNMT), but also by other factors such as histone modification, diet and environment and RNA interference, etc. DNA methylation has an important role in transcriptional regulation, together with histone modification and chromatin remodeling.

Animals↗
PubMed2006

Targeting DNA methylation in cancer.

Cancer growth and metastasis require the coordinate change in gene expression of different sets of genes. While genetic alterations can account for some of these changes, many of the changes in gene expression observed in cancer are caused by epigenetic modifications. The epigenome consists of the chromatin and its modifications, the "histone code" as well as the pattern of distribution of covalent modifications of cytosines residing in the dinucleotide sequence CG by methylation. The normal pattern of distribution of DNA methylation is altered in cancer. A number of genes are regionally hypermethylated but many parts of the genome are hypomethylated. Hypermethylation of tumor suppressor genes is involved in silencing of strategic genes. DNA hypermethylation has received much attention and a number of clinical trials are underway with different inhibitors of DNA methylating enzymes. It is now becoming clear however that hypomethylation also plays a role in cancer by activating genes required for invasion and metastasis. The potential therapeutic implications of targeting DNA methylation in cancer are discussed.

Acetylation↗
PubMed2006

[Advances in the RNA-directed DNA methylation in plants].

The RNA-directed DNA Methylation (RdDM) is one type of epigenetic modification which was firstly discovered in plant. RdDM can directly cause DNA modifications of the genome through RNA-DNA interactions. In plant, both of RdDM and mRNA degradation induced by siRNA can silence sequence specific genes through RNA. They play very significant roles in chromosome rearrangement, defence of virus invasion, regulation of gene expression and many processes of plant development. However, the mechanisms of RdDM are still unclear. In this paper the basic characteristics of RdDM were briefly summarized and advances in studies on mechanisms of RdDM were reviewed. These include the kinds of DNA methyltransferases and their functional mechanisms in RdDM, the relationships between DNA methylation and chromatin modification, and important proteins involved in the RdDM process. In plants, RdDM may occur at both the transcriptional and post-transcriptionnal levels, both of which induce gene silencing. Methylation of the target gene promoter correlates with transcriptional gene silencing (TGS) whereas methylation of the coding sequence is associated with post-transcriptional gene silencing (PTGS). RdDM and RNAi all depend on the similar siRNA and enzymes, such as DCL3, RdR2, SDE4 and AGO4. There are at least three kinds of DNA methyltransferases, DRM1/2, MET1 and CMT3, in pants. They can interact with and modifies all cytidines within the DNA regions homologous to RNA sequence. Furthermore, methylation of lysine 9 in Histone H3 can affect the methylation of cytidines.

DNA Methylation↗
PubMed1990

Genome imprinting and development in the mouse.

Development in mammals is influenced by genome imprinting which results in differences in the expression of some homologous maternal and paternal alleles. This process, initiated in the germline, can continue following fertilization with interactions between oocyte cytoplasmic factors and the parental genomes involving modifier genes. Further epigenetic modifications may follow to render the 'imprints' heritable through subsequent cell divisions during development. Imprinting of genes can be critical for their dosage affecting embryonic growth, cell proliferation and differentiation. The cumulative effects of all the imprinted genes are observed in androgenones (AG) and parthenogenones (PG), which reveal complementary phenotypes with respect to embryonic and extraembryonic tissues. The presence of PG cells in chimeras causes growth retardation, while that of AG cells enhanced growth. AG cells apparently have a higher cell proliferation rate and, unlike PG cells, are less prone to selective elimination. However, the PG germ cells are exempt from cell selection. In chimeras, PG cells are more likely to be found in ectodermal derivatives such as epidermis and brain in contrast to AG cells which make pronounced contributions to many mesodermal derivatives such as muscle, kidney, dermis and skeleton. The presence of androgenetic cells in chimeras also results in the disproportionate elongation of the anterior-posterior axis and sometimes in the abnormal development of skeletal elements along the axis. Genetic studies high-light the influence of subsets of imprinted genes, and identify those that are critical for development.

Animals↗
PubMed1990

Genomic imprinting and cancer.

Genomic imprinting results in a functional non-equivalence of parental chromosomes, presumably by epigenetic modification of the genome, and is required for normal mammalian development. In general, reciprocal phenotypes are observed in embryos containing alterations in the dosage of parental chromosomes, for example where both copies of chromosomes or chromosomal regions are derived from one parent. These phenotypes indicate that duplications of maternal chromosomes inhibit embryonic growth and proliferation whereas duplications of the paternal genome result in enhanced cell growth and proliferation. Alterations in the dosage of parental chromosomes have recently been observed in some forms of recessive tumour in man. Here we discuss the role and possible mechanisms of genomic imprinting during embryogenesis and attempt to draw parallels between the parental origin of the loss of heterozygosity observed in some human tumours and the developmental phenotypes that arise in mice with similar distortions of parental origin. These observations strongly implicate genomic imprinting in the genesis of some forms of tumour and, more generally, in the genetic predisposition to cancer.

Animals↗
PubMed1990

Isozymes and the micro organization of organellar structure and function.

One of the most valuable of the wide-ranging attributes of isozymes is the novel insight they allow into some of the most complex aspects of cell biology. The microorganization of subcellular structure and function is one such area, and the present study utilizes the peroxisome as an example of these applications. The biological characteristics of the major enzymic component of this organelle, catalase, have been detailed in mammalian tissues, where the enzyme exhibits a complex heterogeneity, which is due to multiple types of epigenetic modification. The major native multiplicity, however, has been demonstrated as attributable to sialic acid attachment to the enzyme. In studying the compartmentalization of these isozymes within liver cells, the technique of differential extraction with digitonin was employed, and evidence provided which supports the presence of an appreciable proportion of catalase activity in the cytoplasmic compartment. The source of these cytoplasmic isozymes was traced to release from the peroxisome, and the mechanism of this release identified with variations in the content of lysophosphatidyl choline in the peroxisomal membrane. Studies of the association of catalase with the subcellular membranes indicated an appreciable ionic interaction which varied with membrane type and isozyme status. Activity was enhanced in the bound form, providing support for the interpretation of a general protective role of this enzyme against oxidation of membrane components within the cell. Overall, these studies are considered to contribute significantly to current knowledge of the biological role and subcellular localization of catalase in relation to organellar structure and function.

Animals↗
PubMed1988

Patterns of tumor metastasis: organ selectivity in the spread of cancer cells.

More than a century ago, Fuchs recognized that although tumors varied in their propensity for metastasis, there was, as well, discrimination in the different organs of the body, some providing a more fertile soil for growth for specific tumors than others. Paget dramatized this clear distinction between the intrinsic properties of the cancer cell and the properties of the host when he expanded on the analogy between tumors and plants: "When a plant goes to seed, its seeds are carried in all directions; but they can only live and grow if they fall on congenial soil." Paget is almost apologetic as he contrasts the work of those that study the 'seed' to his own work on the 'soil': "The best work in the pathology of cancer is done by those who...are studying the nature of the seed. They are like scientific botanists; and he who turns over the records of cases of cancer is only a ploughman, but his observations of the properties of the soil may also be useful." In a time where the primary emphasis in cancer research is at the level of gene expression, of regulation and of epigenetic modification of the "seed," those individuals, such as Pauli and Lee, who study the properties of the host environment should not be ignored. Not only are the observations of the 'soil' useful, they provide essential information without which we will not be able to understand the nature of the metastatic process.

Cell Adhesion↗
PubMed1986

Stability of the determined state.

During development parts of plants become determined for specific fates which can persist in populations of dividing cells. Students of plant development have tended to favour the view that the determined state is stabilized at the supracellular level. We provide evidence for the alternative view that determination can be inherited at the cellular level. This conclusion is based on the observation that cultured cells derived from the leaf lamina and cortex of the stem of tobacco plants inherit different states of cytokinin requirement. Plant regeneration experiments show that the cytokinin-requiring (C-) state characteristic of leaf cells and the cytokinin autotrophic (C+) state characteristic of cortex cells are stable but not permanent. Progeny of both cell types can give rise to complete plants with tissues exhibiting the cytokinin requirement of comparable tissues of seed grown plants. Pith cells can shift from the C- to the C+ state by a process known as habituation. Evidence is presented that this epigenetic change is stabilized by a positive-feedback mechanism in which cytokinins appear to promote their own biosynthesis. A single dominant, Mendelian gene, H1-2, controls expression of the C- and C+ phenotypes. There are hints that this gene changes state in cultured cells at rates expected for epigenetic modifications. This suggests that the C- and C+ state can also be stabilized by genetic mechanisms.

Cytokinins↗
PubMed1977

Reversal of the neoplastic state in plants.

Crown-gall transformation involves the gradual and progressive activation of several biosynthetic capacities of the normal cell. These changes in cellular heredity, although extremely stable, are nonetheless potentially reversible and leave the cell totipotent. There is growing evidence that tumor-inducing principle is a self-replicating entity similar to a plasmid. Thus, it could be argued that tumor progression involves changes in the number or state of these entities in the cell. Studies of CDF habituation bear directly on this problem. Conversion of a cell division factor (CDF)-requiring normal cell to the CDF-autotrophic state is a key event in transformation. The fact that CDF habituation is progressive, occurs in the absence of agents of bacterial origin, and has an epigenetic basis indicates that it is not necessary to invoke either somatic mutation or the addition of foreign genes to account for tumor stability and progression in crown-gall. This conclusion provides further support for the hypothesis that, in the words of Braun,(78) "... the cancer problem is basically a problem of anomolous differentiation... Neoplastic growth, like developmental processes, stems from epigenetic modifications against a constant cellular genome."

Cell Differentiation↗
PubMed1984

An immunological investigation of catalase in three mammalian species.

An immunological comparison of catalase has been conducted in the mouse, rat and guinea pig. In each of these species, enzyme activity from the peroxisomal compartment was indicated as immunologically distinct from the cytosolic activity, with catalase in the small granule compartment displaying intermediate characteristics. When related to the established data on the biogenetic and degradative changes of catalase in the mouse, the present results support the proposal that peroxisomal alterations, epigenetic modifications and degradative persistence are general characteristics of catalase biology in mammalian species.

Animals↗
PubMedDate not supplied

[Genomic imprinting and human pathology. I. General Part].

Genetical as well as experimental embryology methods have permitted to uncover a very important feature of mammalian embryonic development: it has been shown that female and male genomic complements are differentially imprinted in such a way that contribution of both a maternally and a paternally derived genome are absolutely necessary for the embryo to complete its normal development. The paternal and maternal genomes are not equivalent and have a complementary role during development in mammals. The differences in activity of each parental genome result from an epigenetic modification of the genome during gametogenesis: the parental imprinting. The recent discovery of several mouse and human genes which are imprinted should permit to address new data of some diseases.

Animals↗
PubMed1995

Coordinate regulation of Igf-2 and H19 in cultured cells.

The insulin-like growth factor 2 (Igf-2) and H19 genes are physically linked on mouse distal chromosome 7 and are reciprocally imprinted. We investigated the molecular basis of the parental imprints in somatic cell cultures derived from normal embryos or from their littermates with maternal uniparental disomy for distal chromosome 7 (MatDi7). In normal cells, the two genes appeared to respond to similar regulatory factor(s), since both genes were coordinately up-regulated upon growth arrest and cell clones which had lost expression of one gene had lost expression of the other. However, in a clone of MatDi7 cells (MatDi7 1-1a), which spontaneously began to express the maternally derived copy of Igf-2, Igf-2 and H19 were not coordinately regulated. MatDi7 1-1a cells showed de novo methylation of sites upstream of Igf-2 and also within the H19 promoter, epigenetic modifications normally seen only on the paternal chromosome. The data provide new experimental evidence for previously hypothesized mechanisms suggesting that Igf-2 and H19 are coordinately regulated.

Animals↗
PubMedDate not supplied

[Heredity and environment in the genesis, epigenesis and evolution of the orofacial area].

Genetic and evolutionary aspects of the dento-facial complex are described according to the concept of heredity as a force of preservation for the human species, though ruled by natural selection and by mutational changes. Ontogenesis and growth of the oral structures reflect mutual regulations between genes and environmental factors. Therefore, the authors carry out an analysis of environmental and constitutional factors affecting dental and facial development. Three levels are identified: individual morphogenesis and growth; actual heredity of parietal dento-facial traits; role and meaning of teeth, jaws and temporo-mandibular joint during evolution leading to Homo sapiens sapiens. As far as individual development is concerned, genes provide only the input for initial cell proliferation and/or differentiation. Further on, growth and morphogenesis of oro-facial structures takes place by means of cell-to-cell and cell-to-substrate interactions. The final, structural result is due to reciprocal interactions among developing structures: muscles modify bone, teeth alignment influences bony bases alignment, ecc. Each structure is genetically determined (teeth, bones, muscles) and each structure carries out epigenetic regulations on other structures: no structure is secluded from biological function of the organism. The inheritance of oro-facial "traits", then, is hardly valuable. First of all, "traits" actually do not exist: they are the product of complex, multifactorial biological mechanisms. Moreover, facial characteristics are affected by polygenic regulation, each gene often showing pleiotropic effects. It has been calculated that 85-90% of facial dimensions in due to epigenetic modifications. Evolution and phylogenesis give evidence about the deep environmental influence on oro-facial morphology. Apart from certain molecular features regarding tooth structure (several dental proteins are today the same as those of the first Vertebrates who lived 500 millions of years ago), tooth number, form, and size depend upon environmental factors. Therefore, dentistry has the important task to preserve fundamental characteristics of dentition, and to intercept environmental pathogenetic factors, as dentition represents a precious instrument for the survival of the human species.

Biological Evolution↗
PubMed1995

New concepts in the pathogenesis of drug-induced lupus.

Although the importance of DNA methylation in normal cellular development and hereditary disease states has been appreciated for some time, the role of environmental agents in causing DNA methylation abnormalities and the effects of DNA hypomethylation on T cells have only recently been examined. This review summarizes current knowledge about the role of DNA methylation in regulating T function and gene expression and highlights a novel mechanism causing autoimmunity, in which epigenetic modification of T cell DNA by environmental agents plays an important role in triggering lupus-like diseases. The observations that DNA methylation inhibitors modify gene expression and induce autoreactivity in cloned, Ag-specific CD4+ cells in vitro, that the modified cells cause autoimmunity in vivo, and that similar changes are found in patients with active lupus provide a new approach to understanding how some forms of autoimmunity develop and may lead to new and more effective treatments.

Acetylation↗
PubMed1995

ENDO A cytokeratin expression in the inner cell mass of parthenogenetic mouse embryos.

During the preimplantation period of development, the first cellular polarization and diversification of the mouse embryo occurs. This process starts at the eight-cell stage and is directly driven by the cytoskeleton. Cell polarization finally leads to the first embryonic epithelium, the trophectoderm, characterized by the presence of cytokeratins. It has not been described whether genomic imprinting, an epigenetic modification of certain genes depending on the parent-of-origin, affects preimplantation development. However, implantation is one of the steps in which an exceptionally high mortality rate is observed in mouse parthenogenetic embryos, a phenomenon that may be influenced by a deficiency in trophectoderm differentiation. To assess this possibility we analyzed the expression of various cytoskeletal proteins in late preimplanted embryos. No differences were observed in the expression of microtubules and microfilaments, but surprisingly, the undifferentiated cells of the parthenogenetic inner cell mass showed distinct cytokeratin staining. This anomalous cytoskeleton expression may be considered as one of the earliest manifestation described to date of the effect of genomic imprinting in development.

Animals↗
PubMed1995

Genomic imprinting and cancer.

Imprinting is vital for normal development, and disruption of imprinting mechanisms on syntenic chromosomes gives very similar phenotypes in mouse and humans. In addition, disruption of normal imprinting provides a plausible explanation for preferential LOH in some embryonal tumours. Moreover, there is evidence that in Wilms' tumour, dysregulation of specific imprinted genes may give rise to the cancer phenotype. Many more questions regarding genomic imprinting need to be answered before the associations described in this review can be properly understood. The most basic issues, such as when and how the imprint is established, can still only be speculated upon. Further study of new imprinted genes and the relationship between their domains and differential replication may show us higher control mechanisms than methylation alone. It remains to be seen if these epigenetic modifications are amenable to therapeutic change in the treatment of inherited syndromes and cancer, or if they can be used to assess individuals at risk of disease. Until then it is probably unwise to speculate on a single unifying theory that explains why a subset of the genome shows such a peculiar non-Mendelian form of inheritance.

Alleles↗