Polycomb repressive complex 2 (PRC2) modifies chromatin to maintain genes for other cell types in a repressed state. Loss of PRC2 function causes developmental defects, immunosuppression and cancer. We have previously shown that interaction with RNA prevents PRC2 from associating with chromatin, thereby allowing eviction of PRC2 and activation of repressed genes. How PRC2 interacts with RNA, and why this blocks its interaction with chromatin, are unknown. The aim of this project is to combine genomics, cell biology, and biophysical techniques to reveal how PRC2 binds RNA and to determine the importance if this interaction for cell identity.
1. Schuettengruber, B., Bourbon, H.M., Di Croce, L. & Cavalli, G. Genome Regulation by Polycomb and Trithorax: 70 Years and Counting. Cell 171, 34-57 (2017).
2. Beltran M, Yates CM, Skalska L, Dawson M, Reis FP, Viiri K, Fisher CL, Sibley CR, Ule J, Jenner RG. (2016). The interaction of PRC2 with RNA or chromatin is mutually antagonistic. Genome Res. 26: 896-907.
3. Justin N, Zhang Y, Tarricone C, Martin SR, Chen S, Underwood E, De Marco V, Haire LF, Walker PA, Reinberg D, Wilson JR, Gamblin SJ. (2016). Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2. Nat Commun. 7:11316.
4. Beltran M., Tavares M., Justin N., Khandelwal G., Ambrose A., Foster B.M., Kunzelmann S. Herrero J., Bartke T., Gamblin S.J., Wilson J.R. and Jenner R.G. (2019). G-tract RNA removes Polycomb Repressive Complex 2 from genes. In revision.
5. Skalska L, Beltran M, Ule J, Jenner RG. (2017). Regulatory feedback from nascent RNA to chromatin and transcription. Nat Rev Mol Cell Biol. 18(5):331-337