Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing

Hagar F. Moussa, Daniel Bsteh, Ramesh Yelagandula, Carina Pribitzer, Karin Stecher, Katarina Bartalska, Luca Michetti, Jingkui Wang, Jorge A. Zepeda-Martinez, Ulrich Elling, Jacob I. Stuckey, Lindsey I. James, Stephen V. Frye and Oliver Bell ()
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Hagar F. Moussa: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC)
Daniel Bsteh: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC)
Ramesh Yelagandula: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC)
Carina Pribitzer: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC)
Karin Stecher: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC)
Katarina Bartalska: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC)
Luca Michetti: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC)
Jingkui Wang: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)
Jorge A. Zepeda-Martinez: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC)
Ulrich Elling: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC)
Jacob I. Stuckey: University of North Carolina at Chapel Hill
Lindsey I. James: University of North Carolina at Chapel Hill
Stephen V. Frye: University of North Carolina at Chapel Hill
Oliver Bell: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC)

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract Polycomb group (PcG) proteins play critical roles in the epigenetic inheritance of cell fate. The Polycomb Repressive Complexes PRC1 and PRC2 catalyse distinct chromatin modifications to enforce gene silencing, but how transcriptional repression is propagated through mitotic cell divisions remains a key unresolved question. Using reversible tethering of PcG proteins to ectopic sites in mouse embryonic stem cells, here we show that PRC1 can trigger transcriptional repression and Polycomb-dependent chromatin modifications. We find that canonical PRC1 (cPRC1), but not variant PRC1, maintains gene silencing through cell division upon reversal of tethering. Propagation of gene repression is sustained by cis-acting histone modifications, PRC2-mediated H3K27me3 and cPRC1-mediated H2AK119ub1, promoting a sequence-independent feedback mechanism for PcG protein recruitment. Thus, the distinct PRC1 complexes present in vertebrates can differentially regulate epigenetic maintenance of gene silencing, potentially enabling dynamic heritable responses to complex stimuli. Our findings reveal how PcG repression is potentially inherited in vertebrates.

Date: 2019
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DOI: 10.1038/s41467-019-09628-6

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