A5089464980- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Nuclear Structure and Function
- Retinoids in leukemia and cellular processes
- RNA and protein synthesis mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Gene expression and cancer classification
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Chromosomal and Genetic Variations
- Telomeres, Telomerase, and Senescence
- Sirtuins and Resveratrol in Medicine
- Adipose Tissue and Metabolism
- Meat and Animal Product Quality
- Cancer-related molecular mechanisms research
- Genetic Mapping and Diversity in Plants and Animals
- DNA Repair Mechanisms
- Autophagy in Disease and Therapy
- Metabolism, Diabetes, and Cancer
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- GABA and Rice Research
- Phytochemicals and Antioxidant Activities
- Muscle Physiology and Disorders
University of Saskatchewan
2016-2025
Brunel University of London
2011-2015
Babraham Institute
2008-2012
Oxford Brookes University
2010
University of Oxford
2006-2008
Hospital for Sick Children
2002-2006
Promyelocytic leukemia (PML) bodies have been implicated in a variety of cellular processes, such as cell-cycle regulation, apoptosis, proteolysis, tumor suppression, DNA repair and transcription. Despite this, the function PML is still unknown. Direct indirect evidence supports hypothesis that interact with specific genes or genomic loci. This includes finding stability affected by cell stress changes chromatin structure. also facilitate transcription replication double-stranded viral...
The promyelocytic leukemia (PML) protein has been implicated in many cellular pathways, but it is unclear whether the accumulation of PML and other proteins into nuclear bodies a regulated or random process. In this paper we have used variety physiological stresses, including heat stress, Cd+2 exposure adenovirus E1A expression, as tools to study principles underlying assembly/disassembly, integrity dynamic behavior bodies. Using live-cell imaging immunofluorescence microscopy, observe that...
Although the mechanism of chromosomal segregation is well known, it unclear how other nuclear compartments such as promyelocytic leukemia (PML) bodies partition during mitosis and re-form in G1. We demonstrate that PML via mitotic accumulations protein (MAPPs), which are distinct from their dynamics, biochemistry structure. During lose biochemical components SUMO-1 Sp100. MAPPs also devoid Daxx these changes occur prior to chromatin condensation coincide with loss membrane integrity. highly...
Promyelocytic leukemia (PML) protein is implicated in transcriptional regulation, apoptosis, DNA repair, and tumor suppression. It not known, however, whether PML other components of bodies function within the vicinity or elsewhere nucleoplasm. In this study, we demonstrate that chromatin organization around influences their morphology, dynamics, structural integrity by a SUMO-1-independent mechanism. Following inhibition during early retracts from periphery bodies, coinciding with formation...
We used electron spectroscopic imaging to map nucleoplasmic transcription sites in human cells at unprecedented resolution. HeLa were permeabilised, nascent transcripts extended BrUTP by ∼40 nucleotides and the resulting BrRNA immunolabelled with gold particles before structures viewed. Nascent RNA is almost invariably associated polymorphic nitrogen-rich (but phosphorus-poor) a diameter of ∼87 nm mass 10 MDa (calculated reference nucleosomes known numbers phosphorus nitrogen atoms)....
Hutchinson-Gilford progeria syndrome (HGPS) is a premature ageing that affects children leading to death, usually from heart infarction or strokes, making this similar normative ageing. HGPS commonly caused by mutation in the A-type lamin gene, LMNA (G608G). This leads expression of an aberrant truncated A protein, progerin. Progerin cannot be processed as wild-type pre-lamin and remains farnesylated, its behavior during interphase mitosis. Farnesyltransferase inhibitors prevent accumulation...
Telomerase reverse transcriptase (hTERT) overexpression, a hallmark of most cancers, drives tumorigenesis by enabling limitless replicative potential. Direct targeting hTERT is challenging, necessitating alternative strategies. Through genome-wide synthetic dosage lethality (SDL) screening in cancer models, including patient-derived organoids, we identify FTSJ3, an RNA 2'-O-methyltransferase, as critical vulnerability hTERT-overexpressing cells. FTSJ3 methylates telomeric repeat-containing...
It is well established that phenolic compounds from plant sources impact readouts of cell health such as reduced radical and reactive oxygen species. However, it unclear if specific structures other cellular processes or proteins, the evolutionary conserved deacetylase Sirtuin 1 (SIRT1), combinations interact synergistically to do so. We observed structurally diverse haskap berry phenolics (caffeic acid, cyanidin, kaempferol-3-O-glucoside, gentisic acid) differentially impacted normal...
RNA polymerase II (RNAPII) transcription has been proposed to occur at factories; nuclear focal accumulations of the active, phosphorylated forms RNAPII. The low ratio factories active genes and units suggests that must share factories. Our previous analyses using light microscopy have indicated multiple could same factory. Furthermore, we found a small number specialized containing high levels erythroid-specific factor KLF1 preferentially transcribed network KLF1-regulated genes. Here used...
C.H. Eskiw, N.F. Cope, I. Clay, S. Schoenfelder, T. Nagano and P. Fraser⇓ Laboratory of Chromatin Gene Expression, The Babraham Institute, Cambridge CB22 3AT, United Kingdom Correspondence: peter.fraser{at}bbsrc.ac.uk
In addition to protein coding genes a substantial proportion of mammalian genomes are transcribed. However, most transcriptome studies investigate steady-state mRNA levels, ignoring considerable fraction the transcribed genome. addition, levels influenced by both transcriptional and posttranscriptional mechanisms, thus do not provide clear picture output. Here, using deep sequencing nuclear RNAs (nucRNA-Seq) in parallel with chromatin immunoprecipitation (ChIP-Seq) active RNA polymerase II,...
DNA microarrays and RNA sequencing (RNA-seq) are major technologies for performing high-throughput analysis of transcript abundance. Recently, concerns have been raised regarding the concordance data derived from two techniques. Using cDNA libraries normal human foreskin fibroblasts, we measured changes in abundance as cells transitioned proliferative growth to quiescence using both RNA-seq. The internal reproducibility RNA-seq was greater than that microarray data. Correlations between...
Whereas the PML protein has been reported to have both transcriptional coactivator and corepressor potential, contribution of nuclear body (PML NB) itself regulation is not well understood. Here we demonstrate that plasmid DNA artificially tethered or NB-targeting domain Sp100 preferentially localized NBs. Using tethering technique, targeted a simian virus 40 promoter-driven luciferase reporter NBs, resulting in repression transgene activity. Conversely, cytomegalovirus promoter-containing...
Natural polyphenols are promising anti-aging compounds not only for their antioxidant activity, but also ability to activate specific cellular pathways mediating the aging process. Avenanthramide C (Avn C), found exclusively in oats, is a natural associated with free radical scavenging; however, it how this compound elicits other protective effects. We investigated intracellular activity of Avn and cytoprotective potential normal human skin fibroblasts exposed extracellular stress. reduced...
Yin Yang 1 (YY1) is a multifunctional transcription factor that acts as an activator, repressor, or initiator of numerous cellular and viral genes. Previous studies in tissue culture model systems suggest YY1 plays role development differentiation multiple cell types, but the biological vertebrate oocytes embryos not well understood. Here we analyzed expression, activity, subcellular localization profiles during Xenopus laevis development. Abundant levels mRNA protein were detected early...
Rapamycin is a well-known inhibitor of the Target (TOR) signaling cascade; however, impact this drug on global genome function and organization in normal primary cells poorly understood. To explore impact, we treated human foreskin fibroblasts with rapamycin observed decrease cell proliferation without causing death. Upon treatment chromosomes 18 10 were repositioned to location similar that induced into quiescence by serum reduction. Although changes positioning occurred, comparative...
Abstract Metformin is a widely-used treatment for type 2 diabetes and reported to extend health lifespan as caloric restriction (CR) mimetic. Although the benefits of metformin are well documented, impact this compound on function organization genome in normal tissues unclear. To explore impact, primary human fibroblasts were treated culture with resulting significant decrease cell proliferation without evidence death. Furthermore, induced repositioning chromosomes 10 18 within nuclear...
Abstract The promyelocytic leukemia (PML) protein is an essential component of PML nuclear bodies (PML NBs) frequently lost in cancer. NBs coordinate chromosomal regions via modification proteins that turn may regulate genes the vicinity these bodies. However, few NB-associated have been identified. and can also mTOR cell fate decisions response to cellular stresses. We now demonstrate depletion U2OS cells or TERT-immortalized normal human diploid fibroblasts results decreased expression...