“Our research will help elucidate how deregulation of normal chromatin function leads to diseases such as cancer or neuronal disorders”
Most genetic information in eukaryotic cells is stored within the nucleus in the form of chromatin. Two key mechanisms that regulate the functional state of chromatin in mammals are DNA methylation and the post-translational modification of histone proteins, both of which convey epigenetic information. Chromatin regulatory factors called ‘epigenetic effector molecules’ recognise methylated DNA or modified histones through their different binding domains and subsequently orchestrate biological events.
Since chromatin is a large macromolecular assembly, modifications most likely act in a concerted manner. However, it is still unclear how the information contained in combinatorial modification patterns on DNA and histones is interpreted. Our group investigates how combinations of DNA and histone modifications regulate the activity of chromatin. Employing methods from chemical biology, biochemistry and proteomics, in conjunction with tissue culture and genomic technologies, we study proteins that recognise DNA and histone modification patterns in the context of chromatin.
We focus on identifying new factors that integrate information contained in multiple chromatin modifications on nucleosomes, and understanding how these factors operate at the molecular level. We are particularly interested in molecular mechanisms underlying epigenetic gene regulation events during DNA replication, tumour formation and differentiation.
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Mirabella, A. C., Foster, B. M., & Bartke, T. (2015). Chromatin deregulation in disease. Chromosoma, DOI 10.1007/s00412-015-0530-0.
Bartke, T., Borgel, J., & DiMaggio, P. A. (2013). Proteomics in epigenetics:new perspectives for cancer research. Briefings in Functional Genomics, 12(3), 205–218.
Frangini, A., Sjöberg, M., Roman-Trufero, M., Dharmalingam, G., Haberle, V., Bartke, T., Lenhard, B., Malumbres, M., Vidal, M., & Dillon, N. (2013). The aurora b kinase and the polycomb protein ring1B combine to regulate active promoters in quiescent lymphocytes. Molecular Cell, 51(5), 647–661.
Watson, A. A., Mahajan, P., Mertens, H. D., Deery, M. J., Zhang, W., Pham, P., Du, X., Bartke, T., Zhang, W., Edlich, C., Berridge, G., Chen, Y., Burgess-Brown, N. A., Kouzarides, T., Wiechens, N., Owen-Hughes, T., Svergun, D. I., Gileadi, O., & Laue, E. D. (2012). The PHD and chromo domains regulate the ATPase activity of the human chromatin remodeler CHD4. Journal of Molecular Biology, 422(1), 3–17.
Bartke, T., Vermeulen, M., Xhemalce, B., Robson, S. C., Mann, M., & Kouzarides, T. (2010). Nucleosome-Interacting proteins regulated by DNA and histone methylation. Cell, 143(3), 470–484.
Dawson, M. A., Bannister, A. J., Göttgens, B., Foster, S. D., Bartke, T., Green, A. R., & Kouzarides, T. (2009). JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature, 461(7265), 819–822.
Santos-Rosa, H., Kirmizis, A., Nelson, C., Bartke, T., Saksouk, N., Cote, J., & Kouzarides, T. (2008). Histone h3 tail clipping regulates gene expression. Nature Structural & Molecular Biology, 16(1), 17–22.
Bartke, T., Pohl, C., Pyrowolakis, G., & Jentsch, S. (2004). Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase. Molecular Cell, 14(6), 801–811.