Last week, I discussed the role of epigenetics on gene expression and how this resulted in differences in phenotype. The example of the flowering plant demonstrated an epigenetic adaptation that promoted survival for the organism, but alterations to gene expression aren't always beneficial. Feinberg's (2007) research provides evidence that epigenetics can also lead to disease and possibly cancer. There is a possibility that certain histone modifications affect the way genes are regulated and cause changes in gene expression and function (Feinberg, 2007). This can prevent phenotypic plasticity from occurring normally and results in the cells' inability to modify behaviours based on input from environmental factors (Feinberg, 2007). Cancer is thought to be a result of both a change in the frequency of DNA methylation and other histone modifications (Feinberg, 2007). The decrease of methylation in tumours results in the activation of many growth-promoting genes, like HPV16 of the human papilloma virus which greatly influences cervical cancer (Feinberg, 2007). While some genes are being turned on by loss of DNA methylation, other genes are being turned off by an increase in DNA methylation. As tumour suppressor genes are silenced, genes such as RB in retinoblastoma, can no longer due their job thus allowing the development of cancerous tumours (Feinberg, 2007). Research suggests that progression of cancer in organisms may be a result of other chromatin modifications (Feinberg, 2007). In lymphoma and colorectal cancer there is a histone modification (Feinberg, 2007). Histones play an important role in the packaging of DNA so that different genes can be expressed or silenced. The expression of genes is observed through the phenotype of organisms. The particular modification in lymphoma and colorectal cancer is a missing H4 acetylated Lys-16 and trimethylated Lys-20 which is believed to cause silencing in transcription (Feinberg, 2007). The way these modifications affect whether certain genes are expressed or how they are able to function greatly impacts the response on the cells of the organism. In the examples from Feinberg (2007), these small changes have huge impacts on the organism. Without the normal regulation of genes, cancer and other diseases may result due to the cells' inability to respond to their changing environment.
Reference:
Feinberg, A 2007, 'Phenotypic plasticity and the epigenetics of human disease', Nature, vol. 447, pp. 433- 440.
You are tackling this somewhat difficult topic very well! You’re making it quite easy to understand. In this blog you focus largely on histone modification. Would you explain the major differences between DNA and histone modification, in terms of how they are involved in gene expression? This would be great for your readers to have to compare both mechanisms.
ReplyDeleteDNA methylation is when a methyl group is attached to one of the nucleotides in the DNA sequence. The methylation of the sequence suppresses the gene so that it is no longer expressed. Histones modification is a little bit different. DNA is wrapped around histones so that it can be packaged in the cell. The parts of the DNA that are tightly wound are silenced because transcription cannot occur, while the more exposed parts are expressed. Histones can be modified in multiple ways, including acetylation or methylation, and each of these alterations effects the transcription of that gene. Certain modifications activate transcription while others inhibit it. Depending on how the histone is modified will influence whether that gene will be expressed or silenced.
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