Epigenetics
Epigenetics refers to heritable changes in gene expression that take place without a change in the DNA sequence. The two forms of interrelated genetic mechanisms are DNA methylation and histone covalent modification. People's DNA is methylated at "CpG dinucleotides," changing the genome's sequence (Feinberg, 2004). Repression typically results from transcriptional alteration and aids in keeping the transposable elements silent. This contributes to the genome's stability and the development of the repressive chromatic state.
The Histone Epigenetic Interplay Towards Cancer
Phosphorylation, methylation, and acetylation are the three covalent post-translational modifications that occur to pluralism. Genes that are active are enriched with specific modification enzymes like H3K9ac and H3K4me3 (Santos-Rosa and Caldas, 2005). On the other hand, the genes that are inactive are enriched with modifications enzymes like H3K27me2, H3K9me3, and H3K9me2. Numerous inactive and active genes have histone modifications overlapping patterns. The histone modification aberrant regulation can have an effect on the activity of the gene and thus the existence of oncogenic potential.
Gene Mutations and Epigenetic Changes
Gene mutations in cancer have been linked to inherited cancer syndrome. Besides, the mutations that occur in the genesis of common cancers are identified to be associated with cancer tumor initiation. Particular genetic mutations are related to tumor progression and lead to epigenetic changes. These changes occur when there is no alteration in the DNA sequence and different factors could result in the inducement of changes (Feinberg, 2004). The DNA is thus able to cause cellular transformation. However, the changes that are produced within the epigenome of the cell that undergo transformation is likely to lead to metastasizing. In this case, mutation of the gene initiates cancer and the epigenetic change promotes cancer progression.
Epigenetic Processes and Cancer Initiation
Cancer initiation could also result from Epigenetic processes. Due to this, it becomes likely that the epigenetic change could directly cause the initiation of cancer. Otherwise, the changes that were "already induced in the epigenome could prime the cells in a way" that promotes the transformation cellular upon a subsequent DNA mutagenic event (Zhang and Dent, 2005). Due to this, the component of epigenetic of the cancer initiation is thus entwined intricately along with the genetic component. Alteration of the gene in the process of encoding makes the "epigenetic enzyme" called "histone acetyltransferase" cause a change in the epigenome (Rodenhiser and Mann, 2006). Another factor that is fundamental in cancer initiation is the encoding of the protein which recognizes and binds to the epigenetic marks. They cause enzyme mutations that lead to cancer. Besides, alteration of the epigenome plays a role in cancer initiation. Critically, the modification of histone also causes cancer. Notably, "histone N-terminal tails" are significant in maintaining the stability of chromatin and are "subject to many modifications" (Zhang and Dent, 2005). The modifications could also provide a room for cancer development. For example, histone acetylation opens the chromatin structure and tends to be repressor, and many genes undergo alteration in a variety of cancer. Methylation modification process also implicates cancer while phosphorylation cause cell cycles that are connected to cancer.
DNA Methylation and Cancer
The initial gene alteration occurred in DNA methylation, and this was observed in cancer cells. According to Egger et al. (2004), "Hypermethylation of CpG islands at tumor suppressor genes switches off these genes, whereas global hypomethylation leads to genome instability and inappropriate activation of oncogenes and transposable elements." The genomic DNA methylation levels are sustained by "DNMT enzymes" and balance the cell (Egger et al., 2004). However, when DNMTs are over-expressed, they become related to cancer. Additionally, methylcytosine can mutate in vivo through deamination to give thymine. The mutation is highly implicated in causing cancer.
References
Egger G, Liang G, Aparicio A, Jones PA. (2004). Epigenetics in human disease and prospects for epigenetic therapy. Nature 429:457-463
Feinberg AP. (2004). The epigenetics of cancer etiology. Seminars Cancer Biol. 14:427-432.
Rodenhiser D, Mann M. (2006). Epigenetics and human disease: translating basic biology into clinical applications. C.M.A.J. 174:341-348.
Santos-Rosa H, Caldas C. (2005). Chromatin modifier enzymes, the histone code and cancer. Eur. J. Cancer. 41:2381-2402.
Zhang K, Dent SY. (2005). Histone modifying enzymes and cancer: going beyond histones. J. Cell. Biochem. 96:1137-1144.
