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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Reactivation of a developmentally silenced embryonic globin gene.
Journal article
King AJ. et al, (2021), Nat Commun, 12
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A gain-of-function single nucleotide variant creates a new promoter which acts as an orientation-dependent enhancer-blocker.
Journal article
Bozhilov YK. et al, (2021), Nat Commun, 12
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Defining genome architecture at base-pair resolution
Journal article
Hua P. et al, (2021), Nature
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Enhancers predominantly regulate gene expression during differentiation via transcription initiation.
Journal article
Larke MSC. et al, (2021), Mol Cell, 81, 983 - 997.e7
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Author Correction: Enhancer-promoter interactions and transcription.
Journal article
Higgs DR., (2021), Nat Genet