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Structural biology of epigenetic targets

Structural biology of epigenetic targets

DEPARTMENT

Integrated structural biology

TEAM LEADER

Jean CAVARELLI

Chromatin structure is a major barrier to all nuclear processes and its modulation is essential for correct cell growth. There is now clear evidence that defects in chromatin modulation are responsible for a wide range of diseases, including cancer. Epigenetic modifications have a large impact on chromatin structure, acting in synergy with ATP-dependent remodelers, histone variants and histone chaperones to regulate nuclear mechanisms. By combining state-of-the-art biochemical and crystallographic techniques, we aim to understand chromatin remodeling at the molecular level. Three main targets are the current focus of our research: protein arginine methyltransferases (PRMTs), histone chaperones and histone deacetylases (HDACs). Furthermore, we are also developing structurebased rational approaches to characterize small molecule modulators of the biological activities of our targets since they are frequently involved in human diseases. Our team also participates in collaborative research on several related projects which require our specific expertise. Present collaborations concern the structural studies of complexes of cancer-related targets such as the Translationally Controlled Tumor Protein (TCTP) and the mRNA of human histone H4.

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