Endothelial cells of the heart, the endocardium, are required for myocardial differentiation, ventricular septation, valve formation and later stages of ventricular morphogenesis. Identification of the gene networks that specify endocardial cell differentiation is crucial for understanding mammalian heart development. This project aims to identify the long-range regulatory interactions that underlie endocardial gene expression. Using newly developed methodologies, the student will generate genome-wide promoter interaction libraries from endocardial and endothelial cells. Bioinformatics analyses will identify the interactions to regulatory elements such as enhancers that underlie transcriptional differences between these cell types, to better understand the processes of cellular differentiation.
B Mifsud, F Tavares-Cadete, AN Young, R Sugar, S Schoenfelder, L Ferreira, SW Wingett, S Andrews, W Grey, PA Ewels, B Herman, S Happe, A Higgs, E LeProust, GA Follows, P Fraser, NM Luscombe and CS Osborne. Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C. Nature Genetics. DOI: 10.1038/ng.3286.
S Schoenfelder, M Furlan-Magaril, B Mifsud, F Tavares-Cadete, R Sugar, BM Javierre, T Nagano, Y Katsman, M Sakthidevi, SW Wingett, E Dimitrova, A Dimond, LB Edelman, S Elderkin, K Tabbada, E Darbo, S Andrews, B Herman, A Higgs, E LeProust, CS Osborne, JA Mitchell, NM Luscombe and P Fraser. The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements. Genome Res. 25(4): 582-97.
Prickett, A.R., Barkas, N., McCole, R.B., Hughes, S., Amante, S.M., Schulz, R., and Oakey, R.J. Genomewide and parental allele specific analysis of CTCF and Cohesin binding sites in mouse brain reveals a tissue-specific binding pattern and an association with differentially methylated regions. Genome Res 2013. 23(10):1624-1635. PMID: 23804403
Proudhon C., Duffié R., Ajjan S., Cowley M., Iranzo J., Carbajosa G., Saadeh H., Holland M.H., Oakey R.J., Rakyan V.K., Schulz R. and Bourc’his D. Protection against de novo methylation is instrumental in maintaining parent-of-origin methylation inherited from the gametes. Molecular Cell, 28;47(6):909-20, 2012. PMID: 22902559