Our group is interested in research that connects epigenetics, cell differentiation and cancer. Epigenetic mechanisms control our genome and ensure that every cell expresses a certain set of genes that defines its cell type specificity. Epigenetic control of the genome has to be dynamic and rigid at the same time, to ensure that the cell maintains its function but can adapt to developmental or environmental changes. The flaws in these finely tuned epigenetic mechanisms can be very detrimental and lead to disease states including cancer.
Our research is focused on study of epigenetic control of normal developmental processes, using spermatogenesis (the development and differentiation of male germ cells) as an excellent differentiation model system. On the other hand, we study how epigenetic deregulation is involved in cancer development, examining germ-cell specific epigenetic regulators, that are aberrantly overexpressed in cancer.
Majority of our research is focused around an epigenetic regulator that was discovered in our laboratory, the histone variant H2A.B, that is testis and brain-specific. This histone variant is targeted to the transcription start sites (TSSs) to co-ordinately activates transcription by a chromatin ‘opening’ mechanism. More recently, we showed that H2A.B can directly bind RNA and is involved in pre-mRNA splicing. This was a major paradigm shift because it showed for the first time that a histone could not only interact directly with DNA but also with RNA. To study H2A.B function, we generated a H2A.B KO mouse model and showed that downregulation of H2A.B affects male fertility and brain function. The unique ability of H2A.B histone to interact with DNA and RNA as well as the RNA processing machinery, opens up a whole new field of research that will provide new insights into the epigenetic regulation.
The Cancer and Germ Cell Epigenetics Group closely collaborates with The Chromatin and Translational Regulation group, led by Prof Tremethick. We have a number of current and potential projects that aim to uncover previously unreported mechanisms of epigenetic control coordinated by H2A.B. See JCSMR student projects for details.