A5037946672- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Genomics and Phylogenetic Studies
- Single-cell and spatial transcriptomics
- MicroRNA in disease regulation
- Immunodeficiency and Autoimmune Disorders
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- Pluripotent Stem Cells Research
- Diabetes and associated disorders
- Advanced biosensing and bioanalysis techniques
- Genetics and Neurodevelopmental Disorders
MRC Weatherall Institute of Molecular Medicine
2016-2025
John Radcliffe Hospital
2014-2025
University of Oxford
2014-2021
Marie Curie
2006
Istituto Pasteur
2004-2006
Abstract Fifteen per cent of cancers maintain telomere length independently telomerase by the homologous recombination (HR)-associated alternative lengthening telomeres (ALT) pathway. A unifying feature these tumours are mutations in ATRX. Here we show that expression ectopic ATRX triggers a suppression pathway and shortening. Importantly ATRX-mediated ALT is dependent on histone chaperone DAXX. Re-expression associated with reduction replication fork stalling, known trigger for HR loss MRN...
The chromatin remodeling protein ATRX, which targets tandem repetitive DNA, has been shown to be required for expression of the alpha globin genes, proliferation a variety cellular progenitors, chromosome congression and maintenance telomeres. Mutations in ATRX have recently identified tumours maintain their telomeres by telomerase independent pathway involving homologous recombination thought triggered DNA damage. It is as yet unknown whether there central underlying mechanism associated...
Driven by the necessity to survive environmental pathogens, human immune system has evolved exceptional diversity and plasticity, which several factors contribute including inheritable structural polymorphism of underlying genes. Characterizing this variation is challenging due complexity these loci, contain extensive regions paralogy, segmental duplication high copy-number repeats, but recent progress in long-read sequencing optical mapping techniques suggests problem may now be tractable....
Abstract Individual enhancers are defined as short genomic regulatory elements, bound by transcription factors, and able to activate cell-specific gene expression at a distance, in an orientation-independent manner. Within mammalian genomes, enhancer-like elements may be found individually or within clusters referred locus control regions super-enhancers (SEs). While these behave similarly individual with respect cell specificity, distribution their orientation-dependence has not been...
Numerous developmentally regulated genes in mouse embryonic stem cells (ESCs) are marked by both active (H3K4me3)- and polycomb group (PcG)-mediated repressive (H3K27me3) histone modifications. This bivalent state is thought to be important for transcriptional poising, but the mechanisms that regulate remain incompletely understood. Examining contribution of microRNAs (miRNAs) regulation genes, we found miRNA biogenesis enzyme DICER was required binding PRC2 core components EZH2 SUZ12,...
Summary Nucleosome remodelling complexes play a key role in gene activation response to environmental changes by driving promoter chromatin reach an accessible configuration. They also mediate genome‐wide organization, although their processes other than activation‐related are poorly understood. The Saccharomyces cerevisiae ADH2 represents excellent model for understanding the of structure and regulation. Following glucose depletion, highly positioned nucleosomes destabilized leading...
Congenital dyserythropoietic anaemia type I (CDA-I) is a hereditary caused by biallelic mutations in the widely expressed genes
The chromatin structure of several Saccharomyces cerevisiae ADR1-dependent genes was comparatively analyzed in vivo order to evaluate the role promoter architecture transcriptional control. In repressing conditions (high glucose) a nucleosome particle always obstructs TATA box, immediately adjacent an upstream-located nucleosome-free region containing cluster Adr1 binding sites. Upon derepression box-containing is destabilized according mechanism shared by all studied. transcription factor...
Abstract Transcriptional enhancers regulate gene expression in a developmental-stage and cell-specific manner. They were originally defined as individual regulatory elements that activate regardless of distance orientation to their cognate genes. Genome-wide studies have shown the mammalian enhancer landscape is much more complex, with different classes clusters enhancer-like combining additive, synergistic redundant manners, possibly acting single, integrated elements. These so-called...
Abstract Driven by the necessity to survive environmental pathogens, human immune system has evolved exceptional diversity and plasticity, which several factors contribute including inheritable structural polymorphism of underlying genes. Characterizing this variation is challenging due complexity these loci, contain extensive regions paralogy, segmental duplication high copy-number repeats, but recent progress in long-read sequencing optical mapping techniques suggests problem may now be...