Selected publications

• De Gobbi Marco, Garrick David, Lynch Magnus, Vernimmen Douglas, Hughes Jim R, Goardon Nicolas, Luc Sidinh, Lower Karen M, Sloane-Stanley Jacqueline A, Pina Cristina, Soneji Shamit, Renella Raffaele, Enver Tariq, Taylor Stephen, Jacobsen Sten EW, Vyas Paresh, Gibbons Richard J, and Higgs Douglas R (2011) Generation of bivalent chromatin domains during cell fate decisions. Epigenetics Chromatin, 4(1):9.

• Law Martin J, Lower Karen M, Voon Hsiao PJ, Hughes Jim R, Garrick David, Viprakasit Vip, Mitson Matthew, De Gobbi Marco, Marra Marco, Morris Andrew, Abbott Aaron, Wilder Steven P, Taylor Stephen, Santos Guilherme M, Cross Joe, Ayyub Helena, Jones Steven, Ragoussis Jiannis, Rhodes Daniela, Dunham Ian, Higgs Douglas R, and Gibbons Richard J (2010) ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner. Cell, 143(3):367-78.

• Wallace Helen AC, Marques-Kranc Fatima, Richardson Melville, Luna-Crespo Francisco, Sharpe Jackie A, Hughes Jim, Wood William G, Higgs Douglas R, and Smith Andrew JH (2007) Manipulating the mouse genome to engineer precise functional syntenic replacements with human sequence. Cell, 128(1):197-209.

• De Gobbi Marco, Viprakasit Vip, Hughes Jim R, Fisher Chris, Buckle Veronica J, Ayyub Helena, Gibbons Richard J, Vernimmen Douglas, Yoshinaga Yuko, de Jong Pieter, Cheng Jan-Fang, Rubin Edward M, Wood William G, Bowden Don, and Higgs Douglas R (2006) A regulatory SNP causes a human genetic disease by creating a new transcriptional promoter. Science, 312(5777):1215-7.

• Gibbons Richard J, Pellagatti Andrea, Garrick David, Wood William G, Malik Nicola, Ayyub Helena, Langford Cordelia, Boultwood Jacqueline, Wainscoat James S, and Higgs Douglas R (2003) Identification of acquired somatic mutations in the gene encoding chromatin-remodeling factor ATRX in the alpha-thalassemia myelodysplasia syndrome (ATMDS). Nat Genet, 34(4):446-9.

At the present time we do not understand the mechanisms by which any mammalian gene is switched on and off during differentiation and development.  Clearly this involves the interaction of key cis-elements (e.g. enhancers, promoters and silencers) with trans-acting proteins (e.g. transcription factors, coactivators, adaptors and chromatin modifiers) that give rise to changes in gene expression, associated with changes in epigenetic modification (methylation, replication, histone acetylation and nuclear position).  We now need to understand the hierarchy and order of these events in gene regulation.

We are studying activation and silencing of the α globin cluster in its natural chromosome environment during erythropoiesis as a model of mammalian gene expression.

We are defining the extent of its chromosomal domain, the critical cis acting sequences and the associated epigenetic modifications, that occur in differentiation and development.   To do this we also study the transcription factors (e.g. GATA-1, NF-E2, SP1) silencing complexes (e.g. Polycomb) and chromatin associated proteins (e.g. ATRX) that regulate expression.

Our ultimate aim is to develop a global view of how mammalian genes are expressed from their normal chromosomal environment and use this information to improve the management of patients with human genetic disease.

Chromosome looping enabling interaction between enhancer and promoter

Microarray analysis characterising epigenetic modifications