During my project I discovered new effects of the ZFP36-family proteins on the regulation of the epigenetic landscape of CD8+ T-lymphocytes. Particularly I found that when we deplete ZFP36-family proteins from mouse T-lymphocytes, there are profound effects on one aspect of T-lymphocyte epigenetics, which is the physical accessibility of DNA sequences throughout the genome. This affects the possibility of proteins that activate or repress a gene to bind the DNA and exert their regulatory function. In fact, we found that these changes in DNA accessibility result in changes of gene expression in T-lymphocytes.
We hypothesise that ZFP36-family RNA-binding proteins affect this aspect of T-lymphocyte epigenetics both directly, by regulating epigenetic factors, and indirectly, by modulating cell metabolism (which can ultimately affect epigenetics). In fact, I found that among the mRNA molecules bound by the ZFP36-family proteins there are many that encode epigenetic proteins and metabolic enzymes.
Moreover, during my project I generated two genetically modified mouse models that will allow us to better understand, from a molecular point of view, how ZFP36-family proteins regulate T-lymphocyte activation.
During the project, my research work was disseminated through an oral presentation at an Immunology Departmental meeting (Babraham Institute) and poster presentations at the RNA UK 2024 meeting and the UK Ageing Research Funders’ Forum Early Career Researchers’ Event. The audience of the two external conferences was not restricted to immunologists, as the first event brought together scientists working with different biological systems with a common interest in RNA research, and the second one also included researchers with non-biological or non-scientific backgrounds. In May 2025 I will present a poster which will include the work I did during my fellowship at the EMBL Conference “Chromatin and epigenetics” in Germany. Once published in a peer-reviewed journal, the results of my research will be open-access, and this will be preceded by submission of the manuscript to a pre-print server. Data and metadata will be available through public repositories. In the future, the results of my work will be exploited also by other scientists and will open new research avenues.
