Douglas R. Higgs

Description

"Understanding the general principles underlying the regulation of gene expression from analysis of a single gene locus" Prof Doug Higgs, The University of Oxford

"Understanding the general principles underlying the regulation of gene expression from analysis of a single gene locus" - We have studied how transcriptional and epigenetic programmes are played out on chromatin spanning the terminal 500kb of human chromosome 16 (16p13.3) as hematopoietic cells undergo lineage fate decisions and differentiation. This region includes the alpha globin cluster and its regulatory elements, which are silenced via the Polycomb system in early progenitors, poised for expression in later progenitors and fully expressed during terminal erythroid differentiation. Other genes in this region are also up-regulated in an erythroid specific manner. Using a variety of approaches we have established the order in which silencing factors are removed, activating transcription factors bind and epigenetic modifications occur. In addition we have shown how chromosomal conformation and nuclear sub-localisation change during hematopoiesis. Natural cis and trans acting mutations (involving transcription factors and chromatin associated proteins) that cause alpha thalassaemia provide additional insight into how the long range regulatory elements may interact with the promoters of the globin genes and other flanking genes to activate their expression. Together these observations establish some of the general principles by which mammalian genes within their natural chromosomal environment are switched on and off during development and differentiation.

Period	12 Nov 2014
Visiting from	MRC Molecular Haematology Unit (United Kingdom)Weatherall Institute for Molecular Medicine (United Kingdom)University of Oxford (United Kingdom)MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford (United Kingdom)