Blue Pill or Red Pill? Epigenetics – the Matrix of the Cell

When a cell divides, its DNA is copied across. Have you ever wondered how this cell knows that it is a liver cell, a muscle cell, or a neuron present in your brain allowing you to process these words? It turns out that the DNA (and in fact its surrounding) in each cell has specific modifications. These changes can be seen as a memory – a cell effectively says: remember you are a liver cell, behave! What these modifications allow, is to control the types and amount of proteins created in the organism. Proteins are the workers of the cell. They are a bit like people. They specify in different disciplines, sometimes they have a specific function, sometimes they have to work with other proteins to make things happen, sometimes they apparently do nothing, and they are all in a network, constantly interacting.

A central dogma of biochemistry states that the DNA (information about our organism coded in combination of 4 bases) is transcribed to RNA (a working form of DNA) and then RNA is translated to proteins (workers of the organism). The process at each step is known to be influenced by various proteins, either by the interactions in the network or by chemical modifications they create. Chemical modifications of the DNA were known and thought to be static, but in early 2000’s scientists discovered that these processes can in fact be reversed. A class of proteins was observed to erase the chemical modifications to the DNA and its surrounding. Following this breakthrough, scientists identified proteins responsible for the reading and writing of the chemical modifications, leading to discovery of the epigenetic code – the “Matrix” of the cell.

Let us consider what this means. If we could alter the “memory” of the cell (i.e. those chemical modifications), we could make cancerous cells forget that they are cancer or maybe even make them die.

It makes it much easier, as many of these control proteins have been found in unnaturally high quantities in various cancers. One of them, called BRD4 – a reader protein, characterises an aggressive rare genetic cancer called NUT midline carcinoma (NMC), with 20 cases in the US each year. In 2010 scientists from Oxford and Harvard developed a compound that inhibits BRD4, called JQ1, named after Jun Qi, the chemist who synthesised it. They tested it for this rare cancer in an extraordinary way: they contacted the patient and with his permission took sample cells from chest fluid draining. They cultured the cancer cells with JQ1 and, to their surprise, the cells started to look normal. Further, mice with NMC treated with JQ1 all survive. Compounds similar to JQ1 are now in clinical trials.

We finally begin to understand the control processes that make cancer what it is. There is much more unexplored biology of readers, writers and erasers, and the more we study them, the more questions we get.

 

About the author

Radek NowakRadek Nowak is a DPhil candidate in Systems Approaches to Biomedical Science at Oxford University. His work focuses on epigenetic erasers, and more generally, crystallography and drug discovery at Structural Genomics Consortium under the supervision of professor Udo Oppermann. In the past Radek has worked on a LHC prototype at Oxford’s Physics Department, spent time at wind energy consultancy and completed a banking internship in the City. Outside of academia he enjoys sailing, swimming and dancing.

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