A5008085628- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- RNA modifications and cancer
- Genetic Syndromes and Imprinting
- CRISPR and Genetic Engineering
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Animal Genetics and Reproduction
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Renal and related cancers
- Prenatal Screening and Diagnostics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Pancreatic function and diabetes
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- HIV Research and Treatment
- Birth, Development, and Health
- Plant Disease Resistance and Genetics
- Cancer-related molecular mechanisms research
Imperial College London
2014-2025
MRC London Institute of Medical Sciences
2017-2025
Hammersmith Hospital
2010-2019
Medical Research Council
2010-2016
MRC Clinical Trials Unit at UCL
2016
The Gurdon Institute
2004-2010
University of Cambridge
2004-2010
Wellcome Trust
2004-2010
Czech Academy of Sciences, Institute of Vertebrate Biology
2010
Royal Children's Hospital
2005
Abstract Summary: Genome‐wide epigenetic reprogramming by demethylation occurs in early mouse embryos and primordial germ cells. In many single‐copy sequences become demethylated both active passive demethylation, whereas imprinted gene methylation remains unaffected. cells are demethylated, presumably demethylation. Here we investigated systematically bisulphite sequencing the profiles of IAP Line1 repeated sequence families during preimplantation cell development. Whereas elements were...
MicroRNAs (miRNAs) have important roles in diverse cellular processes, but little is known about their identity and functions during early mammalian development. Here, we show the effects of loss maternal inheritance miRNAs following specific deletion Dicer from growing oocytes. The mutant mature oocytes were almost entirely depleted all miRNAs, they failed to progress through first cell division, probably because disorganized spindle formation. By comparing single-cell cDNA microarray...
BackgroundMicroRNAs (miRNAs) are critical regulators of transcriptional and post-transcriptional gene silencing, which involved in multiple developmental processes many organisms. Apart from miRNAs, mouse germ cells express another type small RNA, piwi-interacting RNAs (piRNAs). Although it has been clear that piRNAs play a role repression retrotransposons during spermatogenesis, the function miRNA unclear.Methodology/Principal FindingsIn this study, we first revealed expression pattern...
Erasing Markers Epigenetic reprogramming of the mammalian genome, which involves removal and replacement various regulatory epigenetic marks such as DNA methylation, occurs during germ cell differentiation early zygotic development. This process is also critical experimental generation stem cells, but factors pathways that control are not well understood. Hajkova et al. (p. 78 ) investigated erasure methylation development in developing mouse found involved base excision repair (BER)...
Prmt5 , an arginine methyltransferase, has multiple roles in germ cells, and possibly pluripotency. Here we show that loss of function is early embryonic-lethal due to the abrogation pluripotent cells blastocysts. also up-regulated cytoplasm during derivation embryonic stem (ES) together with Stat3, where they persist maintain association Mep50 methylates cytosolic histone H2A (H2AR3me2s) repress differentiation genes ES cells. Loss or results derepression genes, indicating significance...
Highlights•Histone H3/H4 replacement is continuous and mediated by Hira during mouse oogenesis•Loss of results in chromatin abnormalities extensive oocyte loss•Hira depletion reduces histone load, which prevents normal transcriptional regulation•Hira-mediated required for 5mC deposition oocytesSummaryThe integrity chromatin, provides a dynamic template all DNA-related processes eukaryotes, maintained through replication-dependent -independent assembly pathways. To address the role absence...
Cytosine methylation of DNA is a widespread modification that plays numerous critical roles. In the yeast Cryptococcus neoformans, CG occurs in transposon-rich repeats and requires methyltransferase Dnmt5. We show Dnmt5 displays exquisite maintenance-type specificity vitro vivo utilizes similar cofactors as metazoan maintenance methylase Dnmt1. Remarkably, phylogenetic functional analysis revealed ancestral species lost gene for de novo methylase, DnmtX, between 50–150 mya. examined how has...
Reactive oxygen species (ROS)-induced oxidative stress is well known to play a major role in male infertility. Sperm are sensitive ROS damaging effects because as germ cells form mature sperm they progressively lose the ability repair DNA damage. However, how lesions affect early embryonic development remains elusive. Using cattle model, we show that fertilization using exposed caused developmental arrest at time of genome activation. The levels damage response did not directly correlate...
Methylation at the 5 position of cytosine in DNA (5meC) is a key epigenetic mark eukaryotes. Once introduced, 5meC can be maintained through replication by activity ‘maintenance’ methyltransferases (DNMTs). Despite their ancient origin, methylation pathways differ widely across animals, such that either confined to transcribed genes or lost altogether several lineages. We used comparative epigenomics investigate evolution methylation. Although model nematode Caenorhabditis elegans lacks...
Epigenomic mechanisms regulate distinct aspects of the inflammatory response in immune cells. Despite central role for microglia neuroinflammation and neurodegeneration, little is known about their epigenomic regulation response. Here, we show that Ten-eleven translocation 2 (TET2) methylcytosine dioxygenase expression increased upon stimulation with various inflammogens through a NF-κB-dependent pathway. We found TET2 regulates early gene transcriptional changes, leading to metabolic...
Abstract DNA methylation is a critical epigenetic mark in mammalian cells. Many aspects of maintenance have been characterized; however, the exact kinetics post-replicative remain subject debate. Here we develop isolation by 5-ethynyl-deoxyuridine labelling for mass spectrometry (iDEMS), highly sensitive, quantitative spectrometry-based method measuring modifications on metabolically labelled DNA. iDEMS reveals an unexpectedly hemi-methylated landscape nascent Combining with metabolic that...
Genomic imprinting directs the allele-specific marking and expression of loci according to their parental origin. Differential DNA methylation at imprinted control regions (ICRs) is established in gametes and, although largely preserved through development, can be experimentally reset by fusing somatic cells with embryonic germ cell (EGC) lines. Here, we show that Ten-Eleven Translocation proteins Tet1 Tet2 participate efficient erasure imprints this model system. The fusion B EGCs initiates...
Abstract Background Patients with haematological malignancies are often vitamin C deficient, and is essential for the TET-induced conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), first step in active DNA demethylation. Here, we investigate whether oral supplementation can correct deficiency affect 5hmC/5mC ratio patients myeloid cancers treated methyltransferase inhibitors (DNMTis). Results We conducted a randomized, double-blinded, placebo-controlled pilot trial...