How Does Chromatin Architecture Contribute to Gene Expression Dynamics During Cell Differentiation in Vivo?

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).

Disciplines and Techniques

Project supervisor/s

Professor Albert Basson

Albert's research s is to uncover the function of chromatin remodelling factors in brain development and to understand how mutation of these factors cause neurodevelopment disorders and intellectual disability.

King's College London

Dr. Cameron Osborne

Cameron's research has centred on the long-range interactions of promoters that regulate transcription (Mifsud et al., Nature Genetics, 2015).

King's College University

References

The chromatin remodeling factor CHD7 controls cerebellar development by regulating reelin expression

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.

J Clin Invest. ;127(3):874-887

2017 Mar 1

Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain

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.

Neuron 86: 1369

2015

Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C

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.

Nat Genet 47:598

2015

CHiCAGO: robust detection of DNA looping interactions in Capture Hi-C data

Cairns J, Freire-Pritchett P, Wingett SW, Várnai C, Dimond A, Plagnol V, Zerbino D, Schoenfelder S, Javierre BM, Osborne C, Fraser P, Spivakov M

Genome Biol 15:127

2016

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How Does Chromatin Architecture Contribute to Gene Expression Dynamics During Cell Differentiation in Vivo?