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PreprintCC BY-NCbioRxiv

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

  1. 1MIT

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.

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BibTeX
@misc{huseyin2026dissection,
  title = {{Dissection of Polycomb complexes reveals canonical PRC1-independent 3D chromatin interactions}},
  author = {M. K. Huseyin and S. Kim and J. Toppen and N. P. Blackledge and A. S. Hansen},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.13.758654},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.13.758654v1},
  note = {CC BY-NC},
}
RIS
TY  - UNPB
TI  - Dissection of Polycomb complexes reveals canonical PRC1-independent 3D chromatin interactions
AU  - M. K. Huseyin
AU  - S. Kim
AU  - J. Toppen
AU  - N. P. Blackledge
AU  - A. S. Hansen
PY  - 2026
DA  - 2026/10/13
PB  - bioRxiv
DO  - 10.64898/2026.10.13.758654
UR  - https://www.biorxiv.org/content/10.64898/2026.10.13.758654v1
AB  - 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.
ER  -