Genetic syndromes caused by mutations in chromatin genes usually lead to problems in multiple different organ systems, often including the brain and the heart. We believe that the best way to understand the consequences of these mutations is to study their effects in the specific cell types that they most affect. For that reason, our lab places a particular emphasis on technologies that allow us to directly examine complex mixtures of different cell types within intact tissues.
We use a variety of molecular biology techniques to study the consequences of genetic mutations:
Multiplex-GAM: genome-wide identification of chromatin contacts yields insights overlooked by Hi-C
Beagrie, R. A., Thieme, C. J., Annunziatella, C.,
Baugher, C., Zhang, Y., Schueler, M., Kukalev, A., Kempfer, R.,
Chiariello, A. M., Bianco, S., Li, Y., Davis, T., Scialdone, A.,
Welch, L. R., Nicodemi, M. & Pombo, A (2023).
Nature Methods, 20, pp.1037-1047
Complex multi-enhancer contacts captured by genome architecture mapping.
Beagrie, R. A., Scialdone, A., Schueler, M.,
Kraemer, D. C. A., Chotalia, M., Xie, S. Q.,
Barbieri, M., de Santiago, I., Lavitas, L.,
Branco, M. R., Fraser, J., Dostie, J.,
Game, L., Dillon, N., Edwards, P. A. W.,
Nicodemi, M. & Pombo, A (2017).
Nature, 543, pp.519-524
Dynamics of the 4D genome during in vivo lineage specification and differentiation.
Oudelaar AM*, Beagrie RA*, Gosden M, de Ornellas S,
Georgiades E, Kerry J, Hidalgo D, Carrelha J, Shivalingam A,
El-Sagheer AH, Telenius JM, Brown T, Buckle VJ, Socolovsky M,
Higgs DR & Hughes JR. (2020).
Nature Communications, 11, 2722
Gene activation by metazoan enhancers: Diverse mechanisms stimulate distinct steps of transcription.
Beagrie, R. A. and Pombo, A. (2016).
BioEssays, 38(9), pp.881-893