A5065343005- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- Erythrocyte Function and Pathophysiology
- Cancer-related gene regulation
- RNA modifications and cancer
- Cardiac, Anesthesia and Surgical Outcomes
- Cytokine Signaling Pathways and Interactions
- Assisted Reproductive Technology and Twin Pregnancy
- Genetic Syndromes and Imprinting
- Genetic and Kidney Cyst Diseases
- Liver Disease and Transplantation
- Animal Genetics and Reproduction
- Adipose Tissue and Metabolism
- Medical Imaging Techniques and Applications
- Cardiac Arrest and Resuscitation
- Plant Molecular Biology Research
- Chromosomal and Genetic Variations
- Heat shock proteins research
- Hip and Femur Fractures
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Hemoglobinopathies and Related Disorders
- Pluripotent Stem Cells Research
MRC Weatherall Institute of Molecular Medicine
2016-2021
University of Oxford
2014-2021
Medical Research Council
2018
John Radcliffe Hospital
2018
Radboud University Nijmegen
2012-2013
University of Oslo
1991
Oslo University Hospital
1991
Chromatin modifying activities inherent to polycomb repressive complexes PRC1 and PRC2 play an essential role in gene regulation, cellular differentiation, development. However, the mechanisms by which these recognize their target sites function together form chromatin domains remain poorly understood. Recruitment of has been proposed occur through a hierarchical process, dependent on prior nucleation placement H3K27me3. Here, using de novo targeting assay mouse embryonic stem cells we...
Specific communication between gene promoters and enhancers is critical for accurate regulation of expression. However, it remains unclear how specific interactions multiple regulatory elements contained within a single chromatin domain are coordinated. Recent technological advances which can detect multi-way at alleles provide insights into cooperate or compete transcriptional activation. Here, we use such an approach to investigate the α-globin distributed in mouse model extended include...
During embryonic development, maintenance of cell identity and lineage commitment requires the Polycomb-group PRC2 complex, which catalyzes histone H3 lysine 27 trimethylation (H3K27me3). However, developmental origins this regulation are unknown. Here we show that H3K27me3 enrichment increases from blastula stages onward in embryos Western clawed frog ( Xenopus tropicalis ) within constrained domains strictly defined by sequence. Strikingly, although also binds widely to active enhancers,...
Abstract The α- and β-globin loci harbor developmentally expressed genes, which are silenced throughout post-natal life. Reactivation of these genes may offer therapeutic approaches for the hemoglobinopathies, most common single gene disorders. Here, we address mechanisms regulating embryonically α-like globin, termed ζ-globin. We show that in embryonic erythroid cells, ζ-gene lies within a ~65 kb sub-TAD (topologically associating domain) open, acetylated chromatin interacts with α-globin...
Erythropoiesis is a critical homeostatic process responsible for the production of red blood cells, essential oxygen delivery to tissues. This review provides brief overview erythropoiesis: maturation hematopoietic stem cells circulating cells. We examine role glucocorticoids (GCs) in modulating this process, highlighting how they influence erythroid progenitor proliferation and differentiation through various mechanisms, including transcriptional repression non-genomic pathways. GCs have...
ABSTRACT DNA folding within nuclei is a highly ordered process, with implications for gene regulation and development. An array of chromosome conformation capture (3C) methods have been developed to investigate how packaged interrogate specific interactions. While these use different approaches examine target loci (many-versus-all) or the entire genome (all-versus-all), they all rely on core principle endonuclease digestion proximity-based ligation re-arrange genomic order reflect...
Abstract Mammalian genomes are subdivided into large (50-2000 kb) regions of chromatin referred to as Topologically Associating Domains (TADs or sub-TADs). Chromatin within an individual TAD contacts itself more frequently than with in surrounding TADs thereby directing enhancer-promoter interactions. In many cases, the borders defined by convergently orientated boundary elements associated CCCTC-binding factor (CTCF), which stabilises cohesin complex on and prevents its translocation. This...
Genome manipulation in the mouse via microinjection of CRISPR/Cas9 site-specific nucleases has allowed production time for genetically modified models to be significantly reduced. Successful genome already been reported using Cas9 supplied by a DNA construct, vitro transcribed mRNA and recombinant protein. Recently use transgenic strains mice overexpressing shown facilitate mutagenesis maternal supply zygotes this route may provide an alternative exogenous supply. We have investigated...
Post-heat shock refolding of luciferase requires chaperones. Expression a dominant negative HSF1 mutant (dnHSF1), which among other effects depletes cells HSF1-regulated chaperones, blocked post-heat targeted to the cytoplasm, nucleus, or peroxisomes, while endoplasmic reticulum (ER)-targeted was inhibited by about 50 %. Luciferase in cytoplasm could be partially restored expression HSPA1A and fully both DNAJB1. For full ER luciferase, sufficed. Neither nuclear nor peroxisomal rescued...
Increase in the production of hepatic lymph is a compensatory mechanism known to occur cirrhosis, neoplasia liver, biliary obstruction, and right-sided cardiac decompensation with elevated venous pressure. In lymphostasis, dilated lymphatics are reflected on CT as low attenuation rims--perivascular lucencies (PVLs)--surrounding portal veins intrahepatic vena cava. this study, scans livers normal controls patients each four disease categories mentioned above were evaluated for presence PVLs;...
Abstract The promoters of mammalian genes are commonly regulated by multiple distal enhancers, which physically interact within discrete chromatin domains. How such domains form and how the regulatory elements them single cells is not understood. To address this we developed Tri-C, a new Chromosome Conformation Capture (3C) approach to identify concurrent interactions at individual alleles cells. heterogeneity observed between shows that CTCF-mediated formation dynamic processes....
Abstract Specific communication between gene promoters and enhancers is critical for accurate regulation of expression. However, it remains unclear how specific interactions multiple regulatory elements genes contained within a single chromatin domain are coordinated. Recent technological advances allow the investigation multi-way at alleles in individual nuclei. This can provide insights into cooperate or compete transcriptional activation. We have used these techniques mouse model which...