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

H.F. Moussa, D. Bsteh, R. Yelagandula, C. Pribitzer, K. Stecher, K. Bartalska, L. Michetti, J. Wang, J.A. Zepeda-Martinez, U. Elling, J.I. Stuckey, L.I. James, S.V. Frye, O. Bell, Nature Communications 10 (2019).

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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.
Publishing Year
Date Published
2019-04-29
Journal Title
Nature Communications
Volume
10
Issue
1
Article Number
1931
eISSN
IST-REx-ID

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Moussa HF, Bsteh D, Yelagandula R, et al. Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing. Nature Communications. 2019;10(1). doi:10.1038/s41467-019-09628-6
Moussa, H. F., Bsteh, D., Yelagandula, R., Pribitzer, C., Stecher, K., Bartalska, K., … Bell, O. (2019). Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-09628-6
Moussa, Hagar F., Daniel Bsteh, Ramesh Yelagandula, Carina Pribitzer, Karin Stecher, Katarina Bartalska, Luca Michetti, et al. “Canonical PRC1 Controls Sequence-Independent Propagation of Polycomb-Mediated Gene Silencing.” Nature Communications 10, no. 1 (2019). https://doi.org/10.1038/s41467-019-09628-6.
H. F. Moussa et al., “Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing,” Nature Communications, vol. 10, no. 1, 2019.
Moussa HF, Bsteh D, Yelagandula R, Pribitzer C, Stecher K, Bartalska K, Michetti L, Wang J, Zepeda-Martinez JA, Elling U, Stuckey JI, James LI, Frye SV, Bell O. 2019. Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing. Nature Communications. 10(1).
Moussa, Hagar F., et al. “Canonical PRC1 Controls Sequence-Independent Propagation of Polycomb-Mediated Gene Silencing.” Nature Communications, vol. 10, no. 1, 1931, Springer Nature, 2019, doi:10.1038/s41467-019-09628-6.
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