RNA‑driven chromatin and epigenetic programming

Fields of Research

RNA‑driven chromatin and epigenetic programming

Focus

Human cells express tens of thousands of long non-coding RNAs, yet only a fraction have known functions. We study how a subset of these RNAs interact with chromatin and chromatin-associated proteins to organise genomic regulatory elements and maintain epigenetic state.

Our work examines how RNAs position chromatin remodelers, influence enhancer activity, and help re-establish transcriptional programs that preserve cell identity through state transitions. We are particularly interested in how these mechanisms shape the development, maintenance, and regeneration of the cardiovascular system.

Tools

We map RNA–chromatin contacts genome-wide using proximity methods such as Red-C and RADICL-seq. We then relate these interactions to chromatin accessibility, epigenetic marks, and protein binding using CUT&RUN, ATAC-seq, iCLIP, and RNA pulldown mass spectrometry.

High-throughput siRNA libraries provide systematic screening of lncRNA function across cell states. dTAG degron systems allow rapid, reversible protein depletion, which reveals dynamic RNA–protein–chromatin interactions before compensatory responses occur. We complement these molecular approaches with functional endothelial assays, including sprouting angiogenesis, and with MERFISH to map transcript localisation in cardiovascular tissues.

Model

We use endothelial cells to study how RNA–chromatin mechanisms influence proliferation, quiescence, senescence, and regenerative responses. Human pluripotent stem-cell-derived lineages complement this by allowing analysis of chromatin regulation during early differentiation and identity establishment. Cardiac organoids and tissue samples extend these models into complex vascular environments that enable us to connect RNA-mediated genome regulation to cardiovascular health and disease.