DNA Methylation Profile at the DNMT3L Promoter (original) (raw)
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DNA methylation and cancer; A Review Article
Epigenetics is the study of the changes in gene expression that are heritable and do not involve a change in the DNA sequence. DNA methylation is one of the key epigenetic mechanisms that is clearly understood. DNA methylation is the process that add methyl group to the 5 th carbon atom of the cytosine base at CpG dinucleotides without changing the nucleotide sequence. Transcriptional silencing in X inactivation and genomic imprinting are two important epigenetic mechanisms where DNA methylation plays a major role. It is well known that DNA hypermethylation and hypomethylation are directly associated with tumor formation. Hypomethylation leads to the inappropriate and increased levels of gene expression in tumors. Trancriptional repression that is seen in cancers is also mostly due to hypermethylation. DNA methylation plays a major role in transcriptional silencing in X inactivation, genomic imprinting and tumor or cancer formation. Changes in the pattern of DNA methylation have been a consistent finding in cancer cells. DNA methylation plays an important role in the generation of mutations in human tumors. The high incidence of C-toT transitions found in the p53 tumor-suppressor gene. DNA methylation plays a crucial role in the regulation of gene expression and chromatin organization within normal eukaryotic cells. In cancer patterns of DNA methylation are altered with global hypomethylation and hypermethylation of a subset of CpG-dense gene-associated regions (CpG islands).
DNA Methylation and Its Effect on Various Cancers: An Overview
DNA methylation is a normal phenomenon which helps in gene expression, cell differentiation and is an inheritable process. Altered DNA methylation patterns in coding strands lead to epigenetic modification. These epigenetic changes enhances DNA adduct formation, somatic mutations and oncogene activation. During silencing of tumor suppressor genes, various genes/proteins involved in signaling pathways gets disturbed. These changes are reversible but if mutations occur they become irreversible. Hence early detection of these genes/proteins involved in epigenetic alterations may help in decreasing the associated changes in the body.
The role of DNA methylation in cancer development
Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society, 2006
Epigenetic modifications include DNA methylation and covalent modification of histones. These alterations are reversible but very stable and exert a significant impact on the regulation of gene expression. Changes in methylation of promoter or first exon may mimic the effect of mutations of various tumor suppressor genes (TSGs) or protooncogenes. Carcinogenesis can also result from aberrations in genomic DNA methylation that include hypermethylation and hypomethylation of promoter or first exon of cancer-related genes. Hypermethylation of promoter of various TSGs causes their transcriptional silencing. However, hypomethylation of regulatory DNA sequences activates transcription of protooncogenes, retrotransposons, as well as genes encoding proteins involved in genomic instability and malignant cell metastasis. The methylation of genomic DNA in malignant cells is catalyzed by DNA methyltransferases DNMT1 and DNMT3B, revealing significantly elevated expression in different types of ca...
DNA Methylation in Cancer Epigenetics
Epigenetics - Regulation and New Perspectives
DNA methylation is one of the most important epigenetic modifications next to acetylation or histone modifications, as it has a role in the homeostatic control of the cell and is strongly involved in the control of genome expression. DNA methylation, which is catalyzed by DNA methyltransferases (DNMTs), is one of the primary epigenetic mechanisms that control cell proliferation, apoptosis, differentiation, cell cycle, and transformation in eukaryotes. Hypomethylation and hypermethylation result in the activation or repression of genes and in a normal cell there is a strict balance between these processes. Abnormal DNA methylation is a well-known feature of cancer development and progression and can turn normal stem cells into cancer stem cells. Studies clearly show that DNA methylation regulates gene transcription functions in cancer pathogenesis. In cancer cells, DNA methylation patterns are largely modified, and therefore, methylation is used to distinguish cancer cells from norma...
Journal of Clinical Oncology, 2004
DNA methylation acts in concert with other epigenetic mechanisms to regulate normal gene expression and facilitate chromatin organization within cells. Aberrant DNA methylation patterns are acquired during carcinogenic transformation; such events are often accompanied by alterations in chromatin structure at gene regulatory regions. The expression pattern of any given gene is achieved by interacting epigenetic mechanisms. First, the insertion of nucleosomes at transcriptional start sites prevents the binding of the transcriptional machinery and additional cofactors that initiate gene expression. Second, nucleosomes anchor all of the DNMT3A and DNMT3B methyltransferase proteins in the cell, which suggests a role for histone octamers in the establishment of DNA methylation patterns. During carcinogenesis, epigenetic switching and 5-methylcytosine reprogramming result in the aberrant hypermethylation of CpG islands, reducing epigenetic plasticity of critical developmental and tumor suppressor genes, rendering them unresponsive to normal stimuli. Here, we will discuss the importance of both established and novel molecular concepts that may underlie the role of DNA methylation in cancer.
DNA methylation of cancer genome
Birth Defects Research Part C: Embryo Today: Reviews, 2009
DNA methylation plays an important role in regulating normal development and carcinogenesis. Current understanding of the biological roles of DNA methylation is limited to its role in the regulation of gene transcription, genomic imprinting, genomic stability, and X chromosome inactivation. In the past 2 decades, a large number of changes have been identified in cancer epigenomes when compared with normals. These alterations fall into two main categories, namely, hypermethylation of tumor suppressor genes and hypomethylation of oncogenes or heterochromatin, respectively. Aberrant methylation of genes controlling the cell cycle, proliferation, apoptosis, metastasis, drug resistance, and intracellular signaling has been identified in multiple cancer types. Recent advancements in whole-genome analysis of methylome have yielded numerous differentially methylated regions, the functions of which are largely unknown. With the development of high resolution tiling microarrays and high throughput DNA sequencing, more cancer methylomes will be profiled, facilitating the identification of new candidate genes or ncRNAs that are related to oncogenesis, new prognostic markers, and the discovery of new target genes for cancer therapy.
DNA methylation pattern as important epigenetic criterion in cancer
Genetics research international, 2013
Epigenetic modifications can affect the long-term gene expression without any change in nucleotide sequence of the DNA. Epigenetic processes intervene in the cell differentiation, chromatin structure, and activity of genes since the embryonic period. However, disorders in genes' epigenetic pattern can affect the mechanisms such as cell division, apoptosis, and response to the environmental stimuli which may lead to the incidence of different diseases and cancers. Since epigenetic changes may return to their natural state, they could be used as important targets in the treatment of cancer and similar malignancies. The aim of this review is to assess the epigenetic changes in normal and cancerous cells, the causative factors, and epigenetic therapies and treatments.
The DNA methylation and cancer
BioEssays, 2000
There is tremendous ferment in the field of epigenetics as the relationships between chromatin structure and DNA methylation patterns become clearer. Central to this activity is the realization that the 'histone code', which involves the post-translational modification of histones and which has important ramifications for chromatin structure, may be linked to the DNA cytosine methylation pattern. New discoveries have suggested that histone lysine 9 methylation is implicated in the spread of heterochromatin in Drosophila and other organisms. Very recently it has been found that histone lysine 9 methylation is also necessary for some DNA methylation in Neurospora and plants. There is therefore the possibility that these two processes are closely linked, suggesting ways in which DNA methylation patterns may be established during normal development. Understanding these processes is fundamental to understanding what goes awry during the process of aging and carcinogenesis where DNA methylation patterns become substantially altered and contribute to the malignant phenotype.