by Marc Saleme

Created on: August 18, 2009

Epigenetic silencing is a means by which cellular machinery may block certain genes in the DNA sequence from being expressed. Epigenetic silencing of tumor-supressor genes is a relatively ubiquitous cellular mistake which allows the unchecked proliferation of the cell, i.e. cancer. The recognition of this common step, from standard cooperative cell into rogue cell posing a health risk for the individual, opens significant doors for researching novel interventions and even preventions for cancer.

A university-level biology textbook printed in 2002 makes no mention of gene-silencing as a usual suspect in the perpetration of cancer. Only oncogenes and tumor-supressor genes are discussed.

Tumor-supressor genes are code for proteins in the cell which protect against unchecked or faulty proliferation. Oncogenes used to be standard code for proteins which aided normal, healthy cell division, but are now altered such that they are overactive and causing problematic growth signals. Tumor-supressor genes thwart oncogenic havoc, among other deleterious influences, so it's easy to see that if some these systems misbehave in concert, the balance is quickly overturned. It's understood that due to multiple mutations or other genetic missteps, such as these oncogenic activations and homologously dysfunctional tumor-suppressing genes, cancerous conditions are born. Such mutations are effected by chemical carcinogens and physical mutagens such as xrays and certain retroviruses. We now also recognize that many cancerous conditions may be born of gene-silencing rather than mutation.

Gene-silencing, more specifically known as epigenetic silencing is another place where mistakes can cause irregular expression of some stretches of genetic code. The DNA molecule, being extremely long, is copiously organized around helper proteins (histones) to fit into the small cell nucleus, while providing for maximum efficiency of selective gene expression. For a good description of DNA/protein organization relevant to this subject, see this article. DNA segments that are not currently transcribed into products for a particular cell are heavily methylated, blocking sites where transcription proteins might bind. In other words, they are silenced. Additionally, histone proteins have some different traits where DNA is not intended to be transcribed. When the cell requires a certain genetic expression, the appropriate segment of DNA is demethylated, and histones acetylated (among other processes),

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