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

Authors

Huseyin, M. K., Kim, S., Toppen, J., Blackledge, N. P., Hansen, A. S.

Abstract

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.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 15 Oct 2026.

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