Experimental Therapeutics Programme

CNIO - Lilly Epigenetics Section

Head of Section:  María José Barrero
Research highlights

Recent studies have shown that the alterations that take place in cancer cells not only occur at the DNA sequence but also at the level of the epigenome. Eukaryotic DNA is wrapped around histone proteins to constitute chromatin, which plays fundamental structural and regulatory roles. The epigenome consists of chemical changes in both DNA and histones that can be inherited through cell division and are controlled by the action of a large set of epigenetic regulators that possess enzymatic activity. Ultimately, DNA and histone modifications control the level of chromatin condensation, which in turn regulates the accessibility of transcription factors to the chromatin and, therefore, gene expression.

During the past few years several studies, including our own, have suggested that the deregulation of the chromatinmodifying machineries can lead to aberrant gene expression causing cancer and other human diseases. The epigenome is regulated in a highly dynamic fashion by the coordinated action of regulators that are able to write, erase and read histone and DNA modifications (FIGURE). Thus, contrary to genetic mutations, epigenetic aberrations can be reversed by targeting the appropriate epigenetic regulators. Indeed, drugs targeting DNA methyltransferases and histone deacetylases have successfully demonstrated anticancer properties and are currently used in the clinic. Therefore, identifying the molecular function of critical epigenetic regulators and their complex relationship with the cancer epigenome, as well as the development of small molecular inhibitors of their activities, hold great promise for cancer therapy (FIGURE).