Methylation of Gene and its Significance

Honors biology Seminar
Dr. Ashraf
November 16, 2015
This paper main focus is on the methylation of DNA. This paper will define it, give specific examples, and also talk about other types such as hyper methylation. It briefly talks about the role of stem cells in Methylation. It discusses how enzymes take apart of this process, and where it takes place. It briefly discusses the origin and how it happens, and the percentage of how much is found in genomic DNA. It also discusses some of the nucleotides that are part of this process and how they contribute and it discusses the different type of levels that methyl groups are controlled by and how those enzymes work. Lastly, it talks about global methylation and demethylation. This paper\'s purpose is to enlighten people on how methylation works and how it operates to help people have a better understanding of this process. It seems complicated on the outside, but it can be simple if we look at it without intimidation.

DNA methylation is an epigenetic mechanism that occurs by the addition of a methyl (CH3) group to DNA, thereby often modifying the function of the genes. The most widely characterized DNA methylation process is the covalent addition of the methyl group at the 5-carbon of the cytosine ring resulting in 5-methylcytosine (5-mC), also informally known as the "fifth base" of DNA. These methyl groups project into the major groove of DNA and inhibit transcription.

In human DNA, 5-methylcytosine is found in approximately 1.5% of genomic DNA. In somatic cells, 5-mC occurs almost exclusively in the context of paired symmetrical methylation of a CpG site, in which a cytosine nucleotide is located next to a guanidine nucleotide. An exception to this is seen in embryonic stem cells, where a substantial amount of 5-mC is also observed in non-CpG contexts. In the bulk of genomic DNA, most CpG sites are heavily methylated while CpG islands in germ-line tissues and located near promoters of normal somatic cells, remain unmethylated, thus allowing gene expression to occur. When a CpG island in the promoter region of a gene is methylated, expression of the gene is repressed (it is turned off).

The addition of methyl groups is controlled at several different levels in cells and is carried out by a family of enzymes called DNA methyltransferases (DNMTs). Three DNMTs (DNMT1, DNMT3a and DNMT3b) are required for establishment and maintenance of DNA methylation patterns. Two additional enzymes (DNMT2 and DNMT3L) may also have more specialized but related functions. DNMT1 appears to be responsible for the maintenance of established patterns of DNA methylation, while DNMT3a and 3b seem to mediate establishment of new or de novo DNA methylation patterns. Diseased cells such as cancer cells may be different in that DNMT1 alone is not responsible for maintaining normal gene hypermethylation (an increase in global DNA methylation) and both DNMTs 1 and 3b may cooperate for this function.
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.

Cited References