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How does the chromatin regulator PRC2 interact with RNA? Linking transcription with epigenetic state

Richard Jenner Research Image

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.

Disciplines and Techniques
Project supervisor/s
Dr. Richard Jenner
Richard is interested in how transcription factors, chromatin modifiers and nascent RNAs regulate access to the genome to specify and maintain different cell types.
University College London
Dr. Steve Gamblin
Steve is interested in understanding the mode of action of proteins involved in disease by determining their three-dimensional shapes.
University College London
References
Genome Regulation by Polycomb and Trithorax: 70 Years and Counting.
Schuettengruber, B., Bourbon, H.M., Di Croce, L. & Cavalli, G.
Cell 171, 34-57
2017
The interaction of PRC2 with RNA or chromatin is mutually antagonistic.
Beltran M, Yates CM, Skalska L, Dawson M, Reis FP, Viiri K, Fisher CL, Sibley CR, Ule J, Jenner RG.
Genome Res. 26: 896-907
2016
Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2.
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.
Nat Commun. 7:11316
2016
G-tract RNA removes Polycomb Repressive Complex 2 from genes
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.
In revision.
2019
Regulatory feedback from nascent RNA to chromatin and transcription
Skalska L, Beltran M, Ule J, Jenner RG.
Nat Rev Mol Cell Biol. 18(5):331-337
2017