Indispensible epigenetic control of thymic epithelial cell development and function by Polycomb Repressive Complex 2

Thymic T cell development and T cell antigen receptor repertoire selection are dependent on essential molecular cues provided by thymic epithelial cells (TEC), which rely for their development and function on the correct placement of post-translational histone modifications. The repressive H3K27me3 mark is catalyzed by the holoenzyme Polycomb Repressive Complex 2 (PRC2). A TEC-targeted deficiency of PRC2 function results in a hypoplastic thymus compromised in its ability to present antigens and to select a repertoire of T cells with normal effector and regulatory functions. Individual TEC populations are, however, differentially affected in their individual lineage development by the absence of H3K27me3 marks establishing a novel differentiation path that progressively off-sets the shortage of canonical medullary TEC.