Group Leader: Dr Richard Jenner
Each of our cells contains the same genome, the same set of instructions, but exhibit wildly different morphologies and functions. We are interested in how transcription factors, chromatin modifiers and nascent RNAs regulate access to the genome to specify and maintain different cell types. Our research uses embryonic stem cells as a model for embryonic development and T helper cells as a model for adult cell differentiation and is underpinned by our expertise in genomics, bioinformatics and molecular biology methods.
We and others have revealed interactions between the polycomb group of chromatin modifying proteins and RNA. We are seeking to establish the molecular mechanisms and biological significance of polycomb-RNA interactions.
The transcription factors T-bet and GATA3 specify Th1 and Th2 lineages, respectively. We are using this system as a model for understanding how the interplay between antagonistic pairs of transcription factors leads to cell fate decisions.
3. Epigenetic disregulation in Cancer
Cancers exhibit abnormal patterns of chromatin modifications that may contribute to tumourigenesis by fixing cells in a normally transitory differentiation state. We are studying how mutations in polycomb proteins lead to changes to epigenetic state associated with cell transformation.
4. Viral control of host gene expression
Viruses seek to control cellular gene expression to establish a cellular environment conducive to replication and avoid the host anti-viral response. We are identifying the cellular genes directly targeted by viral transcription factors during infection.
Skalska L, Beltran M, Ule J, Jenner RG. (2017). Regulatory feedback from nascent RNA to chromatin and transcription. Nat Rev Mol Cell Biol. 18:331-337
Beltran M., Yates C.M., Skalska L., Dawson M., Reis F.P., Viiri K., Fisher C.L., Sibley C.R., Ule J., Jenner R.G. (2016). The interaction of PRC2 with RNA or chromatin is mutually antagonistic. Genome Res 26: 896-907.
Hertweck A., Evans C.M., Eskandarpour M., Lau J.C., Oleinika K., Jackson I., Kelly A., Ambrose J., Adamson P., Cousins D., Lavender P., Calder V.L., Lord G.M. and Jenner R.G. (2016). T-bet Activates Th1 Genes through Mediator and the Super Elongation Complex. Cell Rep. 15: 2756–2770.
Bouwman R.D., Palser A., Parry C.M., Coulter E., Rasaiyaah R., Kellam P., Jenner R.G. (2014). Human immunodeficiency virus Tat associates with a specific set of cellular RNAs. Retrovirology 11: 53.
Evans C.M. and Jenner R.G. (2013). Transcription factor interplay in T helper cell differentiation. Brief Funct Genomics. doi: 10.1093/bfgp/elt025.
Kanhere A., Hertweck A., Bhatia U., Gokmen R., Perucha, E., Jackson I., Lord G.M., and Jenner R.G. (2012). T-bet and GATA3 orchestrate Th1 and Th2 cell differentiation through lineage-specific targeting of distal regulatory elements. Nature Communications. 3:1268.
Kanhere A., Viiri K., Araújo C.C., Rasaiyaah J., Bouwman R.D., Whyte W.A., Pereira C.F., Brookes E., Walker K., Bell G.W., Pombo A., Fisher A.G., Young R.A. and Jenner R.G. (2010). Short RNAs are transcribed from repressed Polycomb target genes and interact with Polycomb Repressive Complex-2. Mol Cell. 38:675-688.