PHF19 drives PRC2 sub-nuclear compartmentalization to promote motility in TNBC cells [ChIP-seq]

Polycomb Repressive Complex 2 (PRC2), a master regulator of gene expression and chromatin organization, is frequently hijacked in aggressive malignancies such as triple-negative breast cancer (TNBC). Here, we identify a distinct spatial organization of PRC2 in TNBC cells, where the complex assembles into micron-sized nuclear bodies. Using high-resolution spatial proteomics on these endogenous compartments, we identify PHD Finger Protein 19 (PHF19) as the central driver of these structures. We further demonstrate that an intrinsically disordered region (IDR) within PHF19 promotes its clustering into nuclear bodies and link this spatial organization to enhanced cell motility. These findings shed light on a previously unrecognized layer of PRC2 regulation in TNBC cells, demonstrating how its subnuclear compartmentalization, shaped by accessory subunits, orchestrates functional outcomes critical for cancer progression.