A5079475931- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Advanced biosensing and bioanalysis techniques
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- Cell death mechanisms and regulation
- Immunodeficiency and Autoimmune Disorders
- RNA modifications and cancer
- Chronic Lymphocytic Leukemia Research
- Autophagy in Disease and Therapy
- Mesenchymal stem cell research
- Mitochondrial Function and Pathology
- Single-cell and spatial transcriptomics
- Cancer-related gene regulation
- Immunotherapy and Immune Responses
- Genetic Neurodegenerative Diseases
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
University of Essex
2017-2024
William Harvey Research Institute
2024
Queen Mary University of London
2024
University College London
2020-2024
National Hospital for Neurology and Neurosurgery
2024
Genomics (United Kingdom)
2020-2021
Coordinated changes of DNA (de)methylation, nucleosome positioning, and chromatin binding the architectural protein CTCF play an important role for establishing cell-type-specific states during differentiation. To elucidate molecular mechanisms that link these processes, we studied perturbed modification landscape in mouse embryonic stem cells (ESCs) carrying a double knockout (DKO) Tet1 Tet2 dioxygenases. These enzymes are responsible conversion 5-methylcytosine (5mC) into its...
The CCCTC-binding factor (CTCF) organises the genome in 3D through DNA loops and 1D by setting boundaries isolating different chromatin states, but these processes are not well understood. Here we investigate mouse embryonic stem cells, defined regions with decreased Nucleosome Repeat Length (NRL) for ∼20 nucleosomes near CTCF sites, affecting up to 10% of genome. We found that nucleosome-depleted region (NDR) is asymmetrically located >40 nucleotides 5'-upstream from centre motif. strength...
Abstract The mammalian epigenome contains thousands of heterochromatin nanodomains (HNDs) marked by di- and trimethylation histone H3 at lysine 9 (H3K9me2/3), which have a typical size 3–10 nucleosomes. However, what governs HND location extension is only partly understood. Here, we address this issue introducing the chromatin hierarchical lattice framework (ChromHL) that predicts state patterns with single-nucleotide resolution. ChromHL applied to analyse four types in mouse embryonic stem...
Abstract Background Nucleosome repositioning in cancer is believed to cause many changes genome organisation and gene expression. Understanding these important elucidate fundamental aspects of cancer. It also for medical diagnostics based on cell-free DNA (cfDNA), which originates from genomic regions protected digestion by nucleosomes. Results We have generated high-resolution nucleosome maps paired tumour normal tissues the same breast patients using MNase-assisted histone H3 ChIP-seq...
The location of nucleosomes in the human genome determines primary chromatin structure and regulates access to regulatory regions. However, genome-wide information on deregulated nucleosome occupancy its implications cancer cells is scarce. Here, we conducted a comparison high-resolution maps peripheral blood B from patients with chronic lymphocytic leukemia (CLL) healthy individuals at single-base-pair resolution. Our investigation uncovered significant changes positioning CLL. Globally,...
CTCF is an evolutionarily conserved and ubiquitously expressed architectural protein regulating a plethora of cellular functions via different molecular mechanisms. can undergo number post-translational modifications which change its properties functions. One such linked to cancer poly(ADP-ribosyl)ation (PARylation). The highly PARylated form has apparent mass 180 kDa (referred as CTCF180), be distinguished from hypo- non-PARylated with the 130 CTCF130). existing data accumulated so far have...
Abstract Background Histone H1 is the most mobile histone in cell nucleus. Defining positions of on chromatin situ, therefore, represents a challenge. Immunoprecipitation formaldehyde-fixed and sonicated chromatin, followed by DNA sequencing (xChIP-seq), traditionally method for mapping histones onto elements. But since sonication fragmentation precedes ChIP, there consequent loss information about higher-order structure. Here, we present new method, xxChIP-seq, employing antibody binding to...
Abstract The CCCTC-binding factor (CTCF) organises the genome in 3D through DNA loops and 1D by setting boundaries isolating different chromatin states, but these processes are not well understood. Here we focus on relationship between CTCF binding decrease of Nucleosome Repeat Length (NRL) for ∼20 adjacent nucleosomes, affecting up to 10% mouse genome. We found that boundary near is created nucleosome-depleted region (NDR) asymmetrically located >40 nucleotides 5’-upstream from centre...
Abstract Nucleosome repositioning in cancer is believed to cause many changes genome organisation and gene expression. Understanding these important elucidate fundamental aspects of cancer. It also for medical diagnostics based on cell-free DNA (cfDNA), which originates from genomic regions protected digestion by nucleosomes. Here we have generated high resolution nucleosome maps paired tumour normal tissues the same breast patients using MNase-assisted histone H3 ChIP-seq compared them with...
Abstract The mammalian epigenome contains thousands of heterochromatin nanodomains (HNDs) marked by di- and trimethylation histone H3 at lysine 9, which have a typical size 3-10 nucleosomes. However, the (epi)genetic determinants their location boundaries are only partly understood. Here, we compare four HND types in mouse embryonic stem cells, that defined methylases SUV39H1/2 or GLP, transcription factor ADNP chromatin remodeller ATRX. Based on novel hierarchical lattice framework termed...
Abstract Background A CAG repeat expansion in THAP11 was recently found to be associated with spinocerebellar ataxia two Chinese families. Expanded repeats ranged from 45 100 units, CAA sequence interruptions the 5′ region and an uninterrupted tract 3′ tail. Objective Here, we assess population distribution of repeat, its contribution neurological diseases. Methods We interrogated data 54,788 individuals Genomics England, 10,686 patients UCL Queen Square Institute Neurology in‐house database...
Abstract The location of nucleosomes in the human genome determines primary chromatin structure and regulates access to regulatory regions. However, genome-wide information on deregulated nucleosome occupancy its implications cancer cells is scarce. Here, we performed a systematic comparison high-resolution maps peripheral-blood B-cells from patients with chronic lymphocytic leukaemia (CLL) healthy individuals at single base pair resolution. Our investigation uncovered significant changes...
Abstract CTCF is an evolutionarily conserved and ubiquitously expressed architectural protein regulating a plethora of cellular functions via different molecular mechanisms. can undergo number post-translational modifications which change its properties functions. One such linked to cancer poly(ADP-ribosyl)ation (PARylation). The highly PARylated form has apparent mass 180 kDa (referred as CTCF180), be distinguished from hypo- non-PARylated with the 130 CTCF130). existing data accumulated so...
Abstract Mesenchymal stem cells (MSCs) are part of the tumour microenvironment and have been implicated in progression. We found number MSCs significantly increased tumour-burdened mice driven by Fas-threshold signalling. Consequently, lacking Fas lost their ability to induce metastasis development a pancreatic cancer model. Mixing with led sustained production pro-metastatic cytokines CCL2 IL6 cells. The levels these depended on MSCs, linking Fas-mediated MSC-proliferation capacity promote...