A5070565000- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Genetic Syndromes and Imprinting
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- Hematopoietic Stem Cell Transplantation
- Plant Gene Expression Analysis
- Mesenchymal stem cell research
- Immune cells in cancer
- Chromatin Remodeling and Cancer
- Molecular Biology Techniques and Applications
- CAR-T cell therapy research
- Nuclear Receptors and Signaling
- Fungal and yeast genetics research
- Plant Virus Research Studies
- Genomic variations and chromosomal abnormalities
- Retinal Development and Disorders
- Plant Molecular Biology Research
- Plant nutrient uptake and metabolism
- Immune Response and Inflammation
University of Glasgow
2005-2024
Western Infirmary
2004-2012
National Institutes of Health
1999-2010
National Institute of Diabetes and Digestive and Kidney Diseases
2000-2010
Dana-Farber Cancer Institute
2004
Newcastle University
1997-2003
Hope College
2002
Human Genome Sciences (United States)
2002
The 1.2-kb DNA sequence element (5'HS4) at the 5' end of chicken beta-globin locus has two defining properties an insulator: it prevents "external" enhancer from acting on a promoter when placed between them ("enhancer blocking") and acts as barrier to chromosomal position effect (CPE) surrounds stably integrated reporter. We previously reported that single CTCF-binding site in 5'HS4 is necessary sufficient for blocking. show here 250-bp "core" within confer protection against silencing...
AbstractA binding site for the transcription factor CTCF is responsible enhancer-blocking activity in a variety of vertebrate insulators, including insulators at 5′ and 3′ chromatin boundaries chicken β-globin locus. To date, no functional domain have been defined mammalian loci, which are embedded within arrays olfactory receptor genes. In an attempt to define boundary elements that could separate these gene clusters, CTCF-binding sites were searched most distal DNase I-hypersensitive (HSs)...
There is growing consensus that genome organization and long-range gene regulation involves partitioning of the into domains distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components these processes as they can establish boundaries between The ability such paradigm β-globin HS4 to block range enhancers spread repressive histone modifications well established. Here we have addressed hypothesis a element in vertebrates should be capable defending from...
Imprinted methylation of the paternal Rasgrf1 allele in mice occurs at a differentially methylated domain (DMD) 30 kbp 5′ promoter. A repeated sequence 3′ DMD regulates imprinted methylation, which is required for expression. Here we identify mechanism by controls imprinting. The an enhancer blocker that binds CTCF methylation-sensitive manner. bound to unmethylated maternal silences binding prevented repeat-mediated allowing Optimal vitro enhancer-blocking activity requires sites. can be...
AbstractThe serum response factor (SRF) and myocyte enhancer 2A (MEF2A) represent two human members of the MADS-box transcription family. Each protein has a distinct biological function which is reflected by specificities proteins for coregulatory partners DNA-binding sites. In this study, we have investigated mechanism DNA binding utilized these related factors. Although SRF MEF2A belong to same family contain domains, their mechanisms differ in several key aspects. contrast dramatic...
The nuclear genomes of vertebrates show a highly organized program DNA replication where GC-rich isochores are replicated early in S-phase, while AT-rich late replicating. regions gene dense and enriched for active transcription, suggesting connection between regulation timing. Insulator elements can organize independent domains transcription suitable candidates being key regulators We have tested the impact inserting strong origin flanked by β-globin HS4 insulator on timing naturally...
Abstract Long-term reconstituting haematopoietic stem cells (LT-HSCs) are used to treat blood disorders via cell transplantation. The very low abundance of LT-HSCs and their rapid differentiation during in vitro culture hinders clinical utility. Previous developments using stromal feeder layers, defined media cocktails, bioengineering have enabled HSC expansion culture, but mostly short-term HSCs progenitor populations at the expense naive LT-HSCs. Here, we report creation a bioengineered...
Members of the MADS-box family transcription factors are found in eukaryotes ranging from yeast to humans. In plants, proteins regulate several developmental processes including flower, fruit and root development. We have investigated DNA-binding mechanisms used by four such Antirrhinum majus, SQUA, PLE, DEF GLO. SQUA differs characterised mammalian as it can efficiently bind two different classes site. induces bending these binding sites sequence site plays a role determining magnitude...
Genomic maps of chromatin modifications have provided evidence for the partitioning genomes into domains distinct states, which assist coordinated gene regulation. The maintenance domain integrity can require setting boundaries. HS4 insulator element marks 3′ boundary a heterochromatin region located upstream chicken β-globin cluster. Here we show that recruits E3 ligase RNF20/BRE1A to mediate H2B mono-ubiquitination (H2Bub1) at this insulator. Knockdown experiments RNF20 is required H2Bub1...
Abstract Background Members of the HMGN protein family modulate chromatin structure and influence epigenetic modifications. HMGN1 HMGN2 are highly expressed during early development in neural stem/progenitor cells developing adult brain. Here, we investigate whether proteins contribute to plasticity regulation that is essential for maintaining pluripotency stem cells. Results We show loss Hmgn1 or Hmgn2 pluripotent embryonal carcinoma leads increased levels spontaneous neuronal...
Abstract Leukaemias, driven by mutations in hematopoietic stem cells (HSCs), rely on interactions with the bone marrow (BM) niche and other cell populations such as mesenchymal stromal (MSCs) for growth survival. While chimeric antigen receptor (CAR) T-cell therapy shows promise hematological malignancies, its application to acute myeloid leukaemia (AML) is hindered tumour heterogeneity off-target toxicity. Combining CRISPR-Cas9 gene editing CAR has potential selectively targeting AML while...
Serum response elements (SREs) play important roles in transforming extracellular signals into specific nuclear responses. The SRE-binding protein, serum factor (SRF), plays a pivotal role this process. Several transcription factors have been shown to interact with SRF and thereby create distinct complexes different regulatory potentials. ETS domain Elk-1 is one such protein serves integrate mitogen-activated kinase cascades at SREs. uses short hydrophobic surface presented on the of an...
Abstract Background The field of genome editing has been revolutionized by the development an easily programmable tool, CRISPR–Cas9. Despite its promise, off-target activity Cas9 posed a great disadvantage for purposes causing DNA double strand breaks at locations and unwanted outcomes. Furthermore, gene integration applications, which introduce transgene sequences, transgenes to sites could be harmful, hard detect, reduce faithful efficiency. Method Here we report multicolour fluorescence...