Tridimensional regulatory landscape and genome architecture in metazoans

Ferdinand Marlétaz (primary)
Departments of Genetics, Evolution & Environment
University College London
Alex de Mendoza (secondary)
School of Biological and Chemical Sciences
Queen Mary University of London

Abstract

Regulatory elements interact with the genes they control mediating tridimensional loops of chromatin called the Topological Associated Domains (TADs). These structures are essential during embryonic development, and their disruption can lead to disease. While these structures have been well-characterised in vertebrate models, general principles governing their function and evolution in animals remain elusive. Using the sea urchin as a model for their dynamic yet simpler mode of genome evolution, the project is aimed at investigating the dynamics of TAD boundaries during development, the role of CTCF in the establishment of these loops and the impact of transposable elements and DNA methylation exert on these structures.


References

1. Bonev, B., and Cavalli, G. (2016). Organization and function of the 3D genome. Nat. Rev. Genet. 17, 661–678. Available at: http://dx.doi.org/10.1038/nrg.2016.112.
2. Berthelot, C., Muffato, M., Abecassis, J., and Roest Crollius, H. (2015). The 3D organization of chromatin explains evolutionary fragile genomic regions. Cell Rep. 10, 1913–1924. Available at: http://dx.doi.org/10.1016/j.celrep.2015.02.046.
3. Cui, M., Lin, C.-Y., and Su, Y.-H. (2017). Recent advances in functional perturbation and genome editing techniques in studying sea urchin development. Brief. Funct. Genomics 16, 309–318. Available at: http://dx.doi.org/10.1093/bfgp/elx011.
4. Zhang, Y., Li, T., Preissl, S., Amaral, M.L., Grinstein, J.D., Farah, E.N., Destici, E., Qiu, Y., Hu, R., Lee, A.Y., et al. (2019). Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells. Nat. Genet. 51, 1380–1388. Available at: http://dx.doi.org/10.1038/s41588-019-0479-7.
5. Marlétaz, F., Firbas, P.N., Maeso, I., Tena, J.J., Bogdanovic, O., Perry, M., Wyatt, C.D.R., de la Calle-Mustienes, E., Bertrand, S., Burguera, D., et al. (2018). Amphioxus functional genomics and the origins of vertebrate gene regulation. Nature 564, 64–70. Available at: http://dx.doi.org/10.1038/s41586-018-0734-6.


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
DevelopmentGenetics
Techniques & Approaches
BiochemistryBioinformaticsGeneticsMicroscopy / ElectrophysiologyMolecular Biology