- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- Single-cell and spatial transcriptomics
- DNA Repair Mechanisms
- Genomic variations and chromosomal abnormalities
- Cancer Genomics and Diagnostics
- Genomics and Phylogenetic Studies
- Plant Molecular Biology Research
Human Technopole
2024
MRC Weatherall Institute of Molecular Medicine
2019-2023
University of Oxford
2019-2023
John Radcliffe Hospital
2023
Abstract Mammalian gene expression patterns are controlled by regulatory elements, which interact within topologically associating domains (TADs). The relationship between activation of formation structural chromatin interactions and during development is unclear. Here, we present Tiled-C, a low-input chromosome conformation capture (3C) technique. We use this approach to study architecture at high spatial temporal resolution through in vivo mouse erythroid differentiation. Integrated...
ABSTRACT Enhancers and their target promoters often come into close physical proximity when activated. This may be explained by a variety of mechanisms; most recently via cohesin-mediated chromatin loop extrusion. Despite this compelling hypothesis, acute depletion cohesin does not cause widespread changes in gene expression. We have tested the role extrusion on expression at mouse alpha-globin locus during erythropoiesis. Acute downregulates early but late stages differentiation. When...
Abstract As the structure of genome is analysed at ever increasing resolution it becoming clear that there considerable variation in 3D chromatin architecture across different cell types. It has been proposed this may, part, be due to increased recruitment cohesin activated cis-elements (enhancers and promoters) leading cell-type specific loop extrusion underlying formation new subTADs. Here we show correlates well with presence active enhancers varies an allele-specific manner or absence...
Abstract With the boom in Genome-Wide Association Studies (GWAS), it has become apparent that many disease-associated genetic variants lie non-coding regions of genome. In order to prioritise these and disentangle their functional significance, is important be able accurately classify cis-regulatory elements within Historically, classification relied purely on presence characteristic histone marks, with recent advancements using more sophisticated Hidden Markov Model (HMM)-based approaches....
Assay for transposase-accessible chromatin (ATAC) and immunoprecipitation (ChIP), coupled with next-generation sequencing (NGS), have revolutionized the study of gene regulation. A lack standardization in analysis highly dimensional datasets generated by these techniques has made reproducibility difficult to achieve, leading discrepancies published, processed data. Part this problem is due diverse range bioinformatic tools available types Secondly, a number different are required...
Abstract Mammalian gene expression patterns are controlled by regulatory elements, which interact within Topologically Associating Domains (TADs). The relationship between activation of formation structural chromatin interactions and during development is unclear. We developed Tiled-C, a low-input Chromosome Conformation Capture (3C) approach, to study architecture at high spatial temporal resolution through in vivo mouse erythroid differentiation. Integrated analysis matched accessibility...