Research Activity

Mechanism of enhancer-promoter interactions - Using genome editing, it is possible to insert synthetic labels to track the 3D position of promoters, enhancers, and detect nascent RNA when corresponding binding proteins fused with fluorophores are also expressed. With this approach and advanced microscopy such as 3D super-resolution live-cell imaging, it is possible to understand the causal relationship between chromatin interactions and transcription. We will use this system to understand how EPI are regulated during neuronal differentiation. Moreover, with microscopy, we can measure the residency time of protein complexes and the mobility of the chromatin itself, contributing to understanding the biophysics of the chromatin in differentiating cells.

Mechanism of chromatin regulation - A large variety of chromatin modifications, chromatin loopers, and even transcription of enhancers are known to be involved in EPI. Some examples are the histone modification H3K27Ac, the chromatin loopers YY1 and LDB1, the cohesin motor complex, and eRNAs. However, the precise mechanism by which they participate and contribute to EPI remains unclear. Are they required to establish the interaction or to maintain it? How is this propagated in daughter cells? How long does chromatin memory persist? All of these questions, and more, can be addressed with our biophysics interdisciplinary approach.

Mutations in chromatin regulators, regulatory sequences, and EPI engineering - Mutations in chromatin regulators and regulatory sequences often occur in malignancies and can be cause of neurodevelopmental disorders. To design novel therapeutic approaches, it is first necessary to understand how mutations in regulators or regulatory regions impact the regulation mechanism. Once we identify dysregulated mechanisms or interactions, we can design synthetic ad hoc approaches to engineer EPIs and restore physiological expression levels.