Dna methylation research papers

The biological importance of 5-mC as a major epigenetic modification in phenotype and gene expression has been widely recognized. For example DNA hypomethylation , the decrease in global DNA methylation, is likely caused by methyl-deficiency due to a variety of environmental influences and has been proposed as a molecular marker in multiple biological processes such as cancer. The quantification of 5-mC content or global methylation in diseased or environmentally impacted cells could provide useful information for detection and analysis of disease. Furthermore, the detection of the DNA demethylation intermediate 5-fC in various tissues and cells may also be used as a marker to indicate active DNA demethylation. 5-fC can also be directly excised by thymine DNA glycosylase ( TDG ) to allow subsequent base excision repair ( BER ) processing which converts modified cytosine back to its unmodified state.

We performed the genome-wide DNA methylation profiling of mouse embryonic hearts using methyl-sensitive, tiny fragment enrichment/massively parallel sequencing to determine methylation levels at ACGT sites. The results showed that while global methylation of million ACGT sites in developing hearts remains stable between embryonic day (E) and , a small fraction (2901) of them exhibit differential methylation. Gene Ontology analysis revealed that these sites are enriched at genes involved in heart development. Quantitative real-time PCR analysis of 350 genes with differential DNA methylation showed that the expression of 181 genes is developmentally regulated, and 79 genes have correlative changes between methylation and expression, including hyaluronan synthase 2 (Has2). Required for heart valve formation, Has2 expression in the developing heart valves is downregulated at , accompanied with increased DNA methylation in its enhancer. Genetic knockout further showed that the downregulation of Has2 expression is dependent on DNA methyltransferase 3b, which is co-expressed with Has2 in the forming heart valve region, indicating that the DNA methylation change may contribute to the Has2 enhancer's regulating function.

Later loss of the expression, associated with hypermethylation of promoter CpG island was shown for retinoblastoma (Rb) gene in 10% of patients with sporadic form of retinoblastoma [ 62 ]. Several publications have documented de novo methylation of the CpG island for the cyclin dependent kinase inhibitor p16 in both cancer cell lines and primary tumours [ 63 , 64 ]. The aberrant hypermethylation correlated with the lack of p16 expression in these cells. Treatment of the cell lines with 5-aza-2'-deoxycytidine resulted in the demethylation of p16 promoter and reactivation of p16 expression [ 65 ].

On a molecular level cancer is characterized not only by genetic defects, such as deletions, mutations or translocations, but also by epigenetic lesions. The most important epigenetic mechanisms are DNA methylation, Polycomb/trithorax complexes, histon modifications, non-coding RNAs, and chromosomal territories. These epigenetic mechanisms contribute to a stable modification of gene expression without changes in primary DNA sequence. During the development and progression of human tumours a gene-specific hypermethylation with resulting repression of transcription can occur. At the same time, global hypomethylation can very often be observed which contributes to an increase in chromosomal instability. In tumour pathology, the detection of somatic hMLH1 hypermethylation is important for molecular diagnostics of Lynch syndrome. The detection of MGMT gene methylation is a good prognostic and predictive factor for glioblastoma patients. Performing DNA methylation assays for routine diagnostics requires technical as well as theoretical expertise.

Dna methylation research papers

dna methylation research papers

On a molecular level cancer is characterized not only by genetic defects, such as deletions, mutations or translocations, but also by epigenetic lesions. The most important epigenetic mechanisms are DNA methylation, Polycomb/trithorax complexes, histon modifications, non-coding RNAs, and chromosomal territories. These epigenetic mechanisms contribute to a stable modification of gene expression without changes in primary DNA sequence. During the development and progression of human tumours a gene-specific hypermethylation with resulting repression of transcription can occur. At the same time, global hypomethylation can very often be observed which contributes to an increase in chromosomal instability. In tumour pathology, the detection of somatic hMLH1 hypermethylation is important for molecular diagnostics of Lynch syndrome. The detection of MGMT gene methylation is a good prognostic and predictive factor for glioblastoma patients. Performing DNA methylation assays for routine diagnostics requires technical as well as theoretical expertise.

Media:

dna methylation research papersdna methylation research papersdna methylation research papersdna methylation research papers