Genetics explains phenotypic trait in organisms through presence or absence of specific nucleotide sequence of DNA. However, that does not adequately explain the expression or lack of expression of all genes. That indicates, there are other control mechanism, such as DNA methylation and chromatin modification
Cancer epigenetics is the study of epigenetic modifications to the DNA of cancer cells that do not involve a change in the nucleotide sequence, but instead involve a change in the way the genetic code is expressed.
Mechanism of epigenetics
Epigenetics is the alteration in gene expression (function) without changing the nucleotide sequence. Both activation and inactivation of cancer-associated genes can occur by epigenetic mechanisms. The major players in epigenetic mechanisms of gene regulation are DNA methylation, histone deacetylation, chromatin remodeling, small noncoding RNA expression and gene imprinting.
The addition of a methyl group to cytosine residues directly preceding guanidine (CpG) residues is a common post replicative mark. Most often, these modifications occur in areas of high CpG content, termed CpG islands. CpG islands are found in about 60% of human gene promoters. Hypermethylation tends to mark a silent gene, while hypomethylation is usually associated with gene activity. DNA methylation in humans is carried out by three enzymes: DNA methyltransferase 1 (DNMT1), which maintains parental methylation patterns, and DNMT3A and DNMT3B, which regulate de novo methylation.
Histones are highly alkaline proteins packaged in DNA packets called nucleosome. Histone modifications include lysine methylation, arginine methylation, arginine citrullination, lysine acetylation and Serine/Threonine/Tyrosine phosphorylation. Most histone modifications regulate DNA transcription. The histone methylation can activate or restrict transcription. For example, H3K4, H3K36, and H3K79 are the most important places where their methylation results in transcription of genes, and vice versa, methylation of H3K9, H3K27, and H4K20 is accompanied by silence of transcription. Even the number of methylations is also involved in the regulation of transcription, for example, the monomethylating of lysine in H3K9 activate transcription and its trimethylation causes transcriptional inhibition.
miRs are small noncoding RNAs that are highly processed using specific machinery. Once processed down to mature miRNAs, they are targeted to 3′UTRs of mRNA, where they inhibit the translation of the targeted mRNAs and/or cause those mRNAs to be targeted for degradation. This leads to a decrease in the amount of protein made. Either miRs can be oncogenic or they can have tumor suppressive functions. More recently, a push for diagnostic and prognostic miRs has been established due to the identification of many differentially expressed miRs in cancers as compared with normal tissue.
Epigenetic changes can help determine whether genes are turned on or off and can influence the production of proteins in certain cells, ensuring that only necessary proteins are produced. For example, proteins that promote bone growth are not produced in muscle cells. Patterns of epigenetic modification vary among individuals, different tissues within an individual, and even different cells.
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Journal of Molecular Oncology Research