20224RFLLA

With this proposal we will dissect a novel epigenetic mechanism that regulate T-cell quiescence. Namely, we will describe how LINE1-transcript/NCL/KAP1 complex form chromatin condensates, which genomic regions regulates, and its involvement in 3D genome architecture and chromatin compartmentalization, to maintain T-cells in a quiescent state. The novelty resides both in the dissection of chromatin condensates regulated by phase-transition, and in the molecular players we are identifying, LINE1-transcripts, that are generated by transposable elements, a portion of the genome that in recent years is providing important novel evidence for interpreting human biology. Moreover, we will apply unconventional technologies to identify chromatin condensates and describe their impact on chromatin organization. Finally, it will get close immunology to the field of condensates, opening frontiers to novel therapeutic opportunities.