Long Range Epigenetic Silencing in Cancer

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Epigenetics is a term that describes modification of gene expression without a change to the DNA sequence, through processes that involve chemical changes to the DNA such as DNA methylation and binding of specific proteins. It is now well established that epigenetics plays a major role in cancer development, but one of the important questions still to be resolved is the mechanism that is responsible for epigenetic changes. Our recent work has uncovered a new mechanism of epigenetic gene silencing in cancer that can effect large chromosomal regions. We have found that both methylated and unmethylated genes can be silenced by changes to the pattern of proteins that bind to the DNA in a cancer cell. Our data also indicates that this silencing can be reversed using epigenetic drugs. This finding represents a new paradigm in epigenetic control and has major implications not only on cancer diagnostics but also cancer epigenetic therapy. In this grant we propose to further characterise and understand the mechanism involved in long range epigenetic silencing and to determine its prevalence in cancer. This proposal will shed light onto the process underlying long range epigenetic gene silencing in cancer and will provide potential novel targets for cancer detection, prognosis and therapy.