How does chromatin architecture contribute to gene expression dynamics during cell differentiation in vivo?

Albert Basson (primary)
Craniofacial and Regenerative Biology
King's College London
Cameron Osborne (secondary)
Medical and Molecular Genetics
King's College London


Although in vitro studies have implicated genome reorganisation as a central mechanism coordinating cellular differentiation and cell fate determination during cell differentiation, it has not been possible to study long-range enhancer-promoter reorganisation at a genome-wide level during cell differentiation in vivo. This project brings together a group that has developed novel methods to isolate primary neuronal progenitors from the developing mouse brain along a defined developmental trajectory in vivo (Basson) with a group that has and continues to develop innovative molecular and bioinformatics approaches to study chromatin organisation and promoter-enhancer interactions in the genome (Osborne).


1) Whittaker DE, Riegman KL, Kasah S, Mohan C, Yu T, Sala BP, Hebaishi H, Caruso A, Marques AC, Michetti C, Smachetti ME, Shah A, Sabbioni M, Kulhanci O, Tee WW, Reinberg D, Scattoni ML, Volk H, McGonnell I, Wardle FC, Fernandes C, Basson MA. (2017) The chromatin remodeling factor CHD7 controls cerebellar development by regulating reelin expression. J Clin Invest. 2017 Mar 1;127(3):874-887.

2) Mo A, Mukamel EA, Davis FP, Luo C, Henry GL, Picard S, Urich MA, Nery JR, Sejnowski TJ, Lister R, Eddy SR, Ecker JR, Nathans J. (2015) Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain. Neuron 86: 1369-

3) Mifsud B, Tavares-Cadete F, Young AN, Sugar R, Schoenfelder S, Ferreira L, Wingett SW, Andrews S, Grey W, Ewels PA, Herman B, Happe S, Higgs A, LeProust E, Follows GA, Fraser P, Luscombe NM, Osborne CS. (2015) Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C. Nat Genet 47:598-

4) Cairns J, Freire-Pritchett P, Wingett SW, VĂ¡rnai C, Dimond A, Plagnol V, Zerbino D, Schoenfelder S, Javierre BM, Osborne C, Fraser P, Spivakov M. (2016) CHiCAGO: robust detection of DNA looping interactions in Capture Hi-C data. Genome Biol 15:127

Genes, development and STEM* approaches to biology
Area of Biology
Techniques & Approaches
GeneticsMolecular BiologySimulation / Modelling