Dissection of Polycomb complexes reveals canonical PRC1-independent 3D chromatin interactions

The Polycomb system is an essential regulator of developmental genes which controls chromatin state through histone modifications and 3D chromatin organization. Although Polycomb-mediated histone modification is well understood, how Polycomb-mediated 3D chromatin interactions form remains unclear. To address this gap, we combine comprehensive Polycomb subunit degrons with Region Capture Micro-C, ChIP-seq, nascent transcriptomics, and live-cell imaging of DNA loci and Polycomb bodies. We find that, within canonical Polycomb repressive complex 1 (cPRC1), polyhomeotic proteins are the primary contributors to interactions. In surprising contrast to existing models, we find that Polycomb-mediated interactions persist in the absence of cPRC1, and combined depletion of cPRC1 with individual variant PRC1 and PRC2 complexes indicates that the remaining interactions do not depend on a single complex. These results raise the previously unexplored possibility of a more general mechanism for Polycomb-mediated interactions not requiring cPRC1.