Chromatin Biochemistry and Epigenetics
Research in a Nutshell
All cells in our body have the same genetic information (genes) but only a subset of these genes are active in any given cell. A key feature that controls gene activity is the organisation of DNA into chromatin. Chromatin is a structure containing DNA and histone proteins which packages our genetic information in cells. This packaging can either facilitate or restrict access to underlying DNA, providing a layer of gene regulation above the genetic information alone. This concept is the root of the term Epigenetics – with “Epi” meaning above in Greek.
The epigenetic processes that impact gene activity are fundamental for normal biology and are frequently altered in disease, particularly cancer. Remarkably, 30% of cancer causing mutations affect genes encoding epigenetic and chromatin regulators. This is particularly true in childhood cancers where altered epigenetic regulation appears to be the primary cause of disease. We study the fundamental biochemical mechanisms involved in epigenetic regulation of chromatin structure in childhood cancers. Our goal is to translate mechanistic discoveries of how these processes are altered in cancer cells toward the development of rational therapeutics with a clear basis in underlying disease biology.
|Gerry Brien||Group Leader|
|Anthony Doherty||PhD Student|
|Eimear Lagan||PhD Student|
- Simultaneous disruption of PRC2 and enhancer function underlies histone H3.3-K27M oncogenic activity in human hindbrain neural stem cells: Brien, G. L., Bressan, R. B., Monger, C., Gannon, D., Lagan, E., Doherty, A. M., Healy, E., Neikes, H., Fitzpatrick, D. J., Deevy, O., Grant, V., Marqués-Torrejón, M-A., Alfazema, N., Pollard, S. M. & Bracken, A. P., 22 Jul 2021, In: Nature Genetics. 53, 8, p. 1221-1232 12 p.
- Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancer: Bracken, A. P., Brien, G. L. & Verrijzer, C. P., 1 Aug 2019, In: Genes & Development. 33, 15-16, p. 936-959 24 p.
- Targeting chromatin complexes in fusion protein-driven malignancies: Brien, G. L., Stegmaier, K. & Armstrong, S. A., May 2019, In: Nature Reviews Cancer. 19, 5, p. 255-269 15 p.
- The 3D Genome: EZH2 Comes into the Fold: Brien, G. L. & Bracken, A. P., May 2019, In: Trends in Molecular Medicine. 25, 5, p. 362-365 4 p.
- Targeted degradation of BRD9 reverses oncogenic gene expression in synovial sarcoma: Brien, G. L., Remillard, D., Shi, J., Hemming, M. L., Chabon, J., Wynne, K., Dillon, E. T., Cagney, G., Van Mierlo, G., Baltissen, M. P., Vermeulen, M., Qi, J., Fröhling, S., Gray, N. S., Bradner, J. E., Vakoc, C. R. & Armstrong, S. A., 15 Nov 2018, In: eLIFE. 7
Full publication list can be found on Research Explorer: Gerry Brien — University of Edinburgh Research Explorer
- Professor Steven Pollard, The University of Edinburgh
- Professor Adrian Bracken, Trinity College Dublin
Partners and Funders
- Worldwide Cancer Research
Chromatin, epigenetics, cancer, sarcoma, glioma, leukemia, therapeutics
Chromatin Biochemistry, Gene Expression and Chromatin Mapping, Protein-Protein Interactions, Proteomics, CRISPR Screening, Genome Editing