A5081452566- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Birth, Development, and Health
- RNA modifications and cancer
- Folate and B Vitamins Research
- Prenatal Screening and Diagnostics
- Cancer-related gene regulation
- Genetic and phenotypic traits in livestock
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Genetics and Neurodevelopmental Disorders
- Chromosomal and Genetic Variations
- Long-Term Effects of COVID-19
- Infant Nutrition and Health
- Diet and metabolism studies
- Autophagy in Disease and Therapy
- Metabolism and Genetic Disorders
- Bioinformatics and Genomic Networks
- Adolescent and Pediatric Healthcare
- Telomeres, Telomerase, and Senescence
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Cytomegalovirus and herpesvirus research
- Gestational Diabetes Research and Management
- Pancreatic function and diabetes
University of Ulster
2014-2024
Genomics (United Kingdom)
2020
Abstract Background We previously showed that continued folic acid (FA) supplementation beyond the first trimester of pregnancy appears to have beneficial effects on neurocognitive performance in children followed for up 11 years, but biological mechanism this effect has remained unclear. Using samples from our randomized controlled trial second and third (FASSTT), where significant improvements cognitive psychosocial were demonstrated mothers supplemented with 400 µg/day FA compared...
Periconceptional folic acid (FA) is known to have a protective effect in the prevention of neural tube defects (NTD), leading global recommendations for FA supplementation before and early pregnancy. Maternal folate throughout pregnancy may other roles offspring health, including neurodevelopment cognitive performance childhood. Folate essential C 1 metabolism, network pathways involved several biological processes nucleotide synthesis, DNA repair methylation reactions. The evidence reviewed...
Maternal blood folate concentrations during pregnancy have been previously linked with DNA methylation patterns, but this has done predominantly through observational studies. We showed recently in an epigenetic analysis of the first randomized controlled trial (RCT) folic acid supplementation specifically second and third trimesters (the EpiFASSTT trial) that at some imprinted genes was altered cord samples response to treatment. Here, we report on epigenome-wide screening using Illumina...
Suboptimal status of folate and/or interrelated B vitamins (B
We recently identified a class of neuronal gene inheriting high levels intragenic methylation from the mother and maintaining this through later development. show here that these genes are implicated in basic functions such as post-synaptic signalling, rather than development inherit 5mC, but not 5hmC, mother. 5mC is distributed across body appears to facilitate transcription, transcription reduced DNA methyltransferase I (Dnmt1) knockout embryonic stem cells well fibroblasts treated with...
A functional role for DNA methylation has been well-established at imprinted loci, which inherit uniparentally, most commonly from the mother via oocyte. Many CpG islands not associated with imprinting also oocyte, although significance of this, and common features genes affected, are unclear. We identify two major subclasses these gametic differentially methylated regions (gDMRs), namely those important brain testis function. The gDMRs retain acquired in oocyte through preimplantation...
Assisted reproductive technologies (ART) are widely used to treat fertility issues in humans and for the production of embryos mammalian livestock. The use these techniques, however, is not without consequence as they often associated with inauspicious pre- postnatal outcomes including premature birth, intrauterine growth restriction increased incidence epigenetic disorders human large offspring syndrome cattle. Here, global DNA methylation profiles trophectoderm embryonic discs vitro...
Abstract Intestinal development is compromised in low birth weight (LBW) pigs, negatively impacting their growth, health, and resilience. We investigated the molecular mechanisms of altered intestinal maturation observed neonatal juvenile LBW female piglets by comparing changes morphology, gene expression, methylation versus normal (NBW) piglets. A total 16 LBW/NBW sibling pairs were sacrificed at 0 hours, 8 10 days, weeks age. The gastrointestinal tract was weighed, measured, small...
DNA methylation plays a vital role in the cell, but loss-of-function mutations of maintenance methyltransferase DNMT1 normal human cells are lethal, precluding target identification, and existing hypomorphic lines tumour cells. We generated instead series hTERT-immortalised fibroblasts using stably integrated short hairpin RNA. Approximately two-thirds sites showed demethylation as expected, with one-third showing hypermethylation, targets were shared between three independently derived...
Currently the leading cause of global disability, clinical depression is a heterogeneous condition characterised by low mood, anhedonia and cognitive impairments. Its growing incidence among young people, often co-occurring with self-harm, particular concern. We recently reported very high rates first year university students in Northern Ireland, over 25% meeting criteria, based on DSM IV. However, causes such groups remain unclear, diagnosis hampered lack biological markers. The aim this...
While epigenetic mechanisms such as DNA methylation and histone modification are known to be important for gene suppression, relatively little is still understood about the interplay between these systems. The UHRF1 protein can interact with both repressive chromatin marks, but its primary function in humans has been unclear. To determine what that was, we first established stable knockdowns (KD) normal, immortalized human fibroblasts using targeting shRNA, since CRISPR knockouts (KO) were...
Health organizations and countries around the world have found it difficult to control spread of COVID-19. To minimize future impact on UK National Service improve patient care, there is a pressing need identify individuals who are at higher risk being hospitalized because severe Early targeted work was successful in identifying angiotensin-converting enzyme-2 receptors type II transmembrane serine protease dependency as drivers infection. Although approach highlights key pathways,...
Abstract DNA methylation is pivotal in orchestrating gene expression patterns various mammalian biological processes. Perturbation of the bovine alveolar macrophage (bAM) transcriptome, due to Mycobacterium bovis ( M. ) infection, has been well documented; however, impact this intracellular pathogen on bAM epigenome not determined. Here, whole genome bisulfite sequencing (WGBS) was used assess effect infection methylome. The methylomes infected with were compared those non-infected 24 hours...
Imprinted loci are paradigms of epigenetic regulation and associated with a number genetic disorders in human. A key characteristic imprints is the presence gametic differentially methylated region (gDMR). Previous studies have indicated that DNA methylation lost from gDMRs could not be restored by DNMT1, or de novo enzymes DNMT3A 3B stem cells, indicating imprinted regions must instead undergo passage through germline for reprogramming. However, previous were non-quantitative, unclear on...
DNA methylation microarrays are widely used in clinical epigenetics and often processed using R packages such as ChAMP or RnBeads by trained bioinformaticians. However, looking at specific genes requires bespoke coding for which wet-lab biologists clinicians not trained. This leads to high demands on bioinformaticians, who may lack insight into the biological problem. To bridge this gap, we developed a tool mapping quantification of differences candidate genomic features interest, without...
Abstract Background The human ZFP57 gene is a major regulator of imprinted genes, maintaining DNA methylation marks that distinguish parent-of-origin-specific alleles. the itself has shown sensitivity to environmental stimuli, particularly folate status. However, role in ’s own regulation not been fully investigated. Methods We used samples and data from our previously described randomised controlled trial (RCT) pregnancy called Folic Acid Supplementation Second Third Trimester (FASSTT),...
Abstract Some chemotherapeutic agents which cause loss of DNA methylation have been recently shown to induce a state “viral mimicry” involving upregulation endogenous retroviruses (ERV) and subsequent innate immune response. This approach may be useful in combination with checkpoint cancer therapies, but relatively little is known about normal cellular control ERV suppression. The UHRF1 protein can interact the maintenance DNMT1 play an important role epigenetic cell. To examine potential...
Abstract Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates rodent muscle. Whether can decelerate, or reverse humans unknown. Here, we performed powerful meta-analysis of the methylome transcriptome an unprecedented number human skeletal samples (n = 3,176). We show that: 1) individuals with higher baseline aerobic fitness have younger transcriptomic profiles, 2) leads to...