Research groups
Colleges
Websites
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MRC Molecular Haematology Unit
Research Unit
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MRC Weatherall Institute of Molecular Medicine
Research Institute
Douglas Higgs
Emeritus Professor
- Consultant Physician
The regulation of gene expression during erythropoiesis
Our laboratory is interested in the general question of how mammalian genes are switched on and off during lineage commitment and differentiation. We study genes (e.g. globin) in detail and also study gene expression using genome wide analyses. We study all aspects of gene expression including the key cis-regulatory elements (enhancers, promoters and insulators), the transcription factors and co-factors that bind them, the epigenetic modifications of chromatin and DNA and the role of associated phenomena such as chromosome conformation and nuclear sub-compartmentalisation using imaging techniques. These studies are performed both in cell systems and in model organisms as well as in human patients with various inherited and acquired genetic and epigenetic abnormalities. The translational goal of this work is to develop new ways to modify gene expression during blood formation with the aim of manipulating gene expression and ameliorating the clinical phenotypes of patients with a variety of blood disorders.
Key publications
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Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment.
Journal article
Hughes JR. et al, (2014), Nat Genet, 46, 205 - 212
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ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner.
Journal article
Law MJ. et al, (2010), Cell, 143, 367 - 378
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Manipulating the mouse genome to engineer precise functional syntenic replacements with human sequence.
Journal article
Wallace HAC. et al, (2007), Cell, 128, 197 - 209
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A regulatory SNP causes a human genetic disease by creating a new transcriptional promoter.
Journal article
De Gobbi M. et al, (2006), Science, 312, 1215 - 1217
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Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease.
Journal article
Tufarelli C. et al, (2003), Nat Genet, 34, 157 - 165
Recent publications
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The relationship between genome structure and function.
Journal article
Oudelaar AM. and Higgs DR., (2020), Nat Rev Genet
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The mouse alpha-globin cluster: a paradigm for studying genome regulation and organization.
Journal article
Oudelaar AM. et al, (2020), Curr Opin Genet Dev, 67, 18 - 24
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Loss of Extreme Long-Range Enhancers in Human Neural Crest Drives a Craniofacial Disorder.
Journal article
Long HK. et al, (2020), Cell Stem Cell, 27, 765 - 783.e14
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Recapitulation of erythropoiesis in congenital dyserythropoietic anaemia type I (CDA-I) identifies defects in differentiation and nucleolar abnormalities.
Journal article
Scott C. et al, (2020), Haematologica, Online ahead of print
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A remarkable case of HbH disease illustrates the relative contributions of the α-globin enhancers to gene expression.
Journal article
Badat M. et al, (2020), Blood