A5037385219- RNA modifications and cancer
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Genetics, Aging, and Longevity in Model Organisms
- Genetic Neurodegenerative Diseases
- RNA and protein synthesis mechanisms
- Genomic variations and chromosomal abnormalities
- RNA regulation and disease
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Microbial Metabolic Engineering and Bioproduction
- Microtubule and mitosis dynamics
- Advanced Glycation End Products research
- CRISPR and Genetic Engineering
- Cellular transport and secretion
- 3D Printing in Biomedical Research
- Cell death mechanisms and regulation
- Nutrition, Genetics, and Disease
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neuroblastoma Research and Treatments
- Nuclear Structure and Function
King's College London
2018-2024
Imperial College London
2014-2023
Queen Mary University of London
2021-2023
Medical Research Council
2019-2020
Thrombosis and Atherosclerosis Research Institute
2019
McMaster University
2019
Hammersmith Hospital
2014-2019
MRC London Institute of Medical Sciences
2019
University of Hong Kong
2016-2019
Chinese University of Hong Kong
2019
BackgroundFriedreich's ataxia is a progressive degenerative disorder caused by deficiency of the frataxin protein. Expanded GAA repeats within intron 1 (FXN) gene lead to its heterochromatinisation and transcriptional silencing. Preclinical studies have shown that histone deacetylase inhibitor nicotinamide (vitamin B3) can remodel pathological heterochromatin upregulate expression FXN. We aimed assess epigenetic neurological effects safety high-dose in patients with Friedreich's...
Body mass results from a complex interplay between genetics and environment. Previous studies of the genetic contribution to body have excluded repetitive regions due technical limitations platforms used for population scale studies. Here we apply genome-wide approaches, identifying an association adult copy number (CN) 47S-ribosomal DNA (rDNA). rDNA codes 18 S, 5.8 S 28 ribosomal RNA (rRNA) components ribosome. In mammals, there are hundreds copies these genes. Inter-individual variation in...
Large intronic expansions of the triplet-repeat sequence (GAA.TTC) cause transcriptional repression Frataxin gene (FXN) leading to Friedreich's ataxia (FRDA). We previously found that GAA-triplet stimulate heterochromatinization in vivo transgenic mice. report here using chromosome conformation capture (3C) coupled with high-throughput sequencing GAA-repeat expansion FRDA cells stimulates a higher-order structure as fragment containing showed an increased interaction frequency genomic...
Abstract Background Ribosomal DNA (rDNA) displays substantial inter-individual genetic variation in human and mouse. A systematic analysis of how this impacts epigenetic states expression the rDNA has thus far not been performed. Results Using a combination long- short-read sequencing, we establish that 45S units C57BL/6J mouse strain exist as distinct haplotypes influence state transcriptional output any given unit. methylation dynamics at these are dichotomous life-stage specific: one...
Telomeres are a significant challenge to DNA replication and prone stress telomere fragility. The shelterin component TRF1 facilitates but the molecular mechanism remains uncertain. By interrogating proteomic composition of telomeres, we show that mouse telomeres lacking undergo protein reorganisation associated with recruitment damage response chromatin remodellers. Surprisingly, mTRF1 suppresses accumulation promyelocytic leukemia (PML) protein, BRCA1 SMC5/6 complex at which is increased...
Neuroglobin (NGB) is predominantly expressed in the brain and retina. Studies suggest that NGB exerts protective effects to neuronal cells implicated reducing severity of stroke Alzheimer's disease. However, little known about mechanisms which regulate cell type-specific expression gene. In this study, we hypothesized distal regulatory elements (DREs) are involved optimal By chromosome conformation capture identified two novel DREs located −70 kb upstream +100 downstream from ENCODE database...
SUMMARY Body mass results from a complex interplay between genetics and environment. The contribution of genetic variation to body has been extensively studied, but due the technical limitations platforms used for population scale studies, repetitive parts genome have not previously considered. Here we applied genome-wide approaches identify an association adult copy number (CN) 45S-ribosomal DNA (rDNA). rDNA codes rRNA components ribosome exists in hundreds copies/cell mammals....
Telomeric repeat-containing RNAs are long non-coding generated from the telomeres. TERRAs essential for establishment of heterochromatin marks at telomeres, which serve binding members protein 1 (HP1) family epigenetic modifiers involved with chromatin compaction and gene silencing. While HP1γ is enriched on bodies actively transcribed human mouse genes, it unclear if its transcriptional role important function in telomere cohesion maintenance. We aimed to study effect transcription factors...
Summary Sex differences in growth rate very early embryos have been recognized a variety of mammals and attributed to sex-chromosome complement effects as they occur before overt sexual differentiation. We previously found that complement, rather than sex hormones regulates heterochromatin-mediated silencing transgene autosomal gene expression mice. Here, dimorphism proliferation was investigated. confirm male embryonic fibroblasts proliferate faster female show this advantage is completely...
Abstract Telomeres are a significant challenge to DNA replication and prone stress telomere fragility. The shelterin component TRF1 facilitates but the molecular mechanism remains uncertain. By interrogating proteomic composition of telomeres, we show that telomeres lacking undergo protein reorganisation associated with damage response chromatin remodelers. Surprisingly, suppresses accumulation promyelocytic leukemia (PML) protein, BRCA1 SMC5/6 complex at which is increased Homologous...
Abstract Background Ribosomal DNA (rDNA) displays substantial inter-individual genetic variation in human and mouse. A systematic analysis of how this impacts epigenetic states expression the rDNA has thus far not been performed. Results Using a combination long- short-read sequencing, we establish that 45S units C57BL/6J mouse strain exist as distinct haplotypes influence state transcriptional output any given unit. methylation dynamics at these are dichotomous life-stage specific: one...