A5000117024- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Genetic Syndromes and Imprinting
- Virus-based gene therapy research
- Renal and related cancers
- Prenatal Screening and Diagnostics
- Immunotherapy and Immune Responses
- Biomedical and Engineering Education
- RNA Interference and Gene Delivery
- Viral Infectious Diseases and Gene Expression in Insects
- Plant Molecular Biology Research
- DNA and Nucleic Acid Chemistry
- RNA modifications and cancer
- Genetics, Aging, and Longevity in Model Organisms
- Endoplasmic Reticulum Stress and Disease
- Genomics and Phylogenetic Studies
- CAR-T cell therapy research
- Genomics, phytochemicals, and oxidative stress
- Plant and Fungal Interactions Research
- Cancer Genomics and Diagnostics
- Bacterial Genetics and Biotechnology
- Bartonella species infections research
- Pancreatic function and diabetes
Babraham Institute
2013-2024
Granta Design (United Kingdom)
2023
Friedrich-Alexander-Universität Erlangen-Nürnberg
2003-2007
Medizinische Hochschule Hannover
2005
University of Göttingen
2005
University of California, San Diego
2001
Jeonju University
2001
Texas A&M Health Science Center
1995
Missouri College
1988
University of Missouri
1988
Cohesin is a chromatin-associated protein complex that mediates sister chromatid cohesion by connecting replicated DNA molecules. also has important roles in gene regulation, but the mechanistic basis of this function poorly understood. In mammalian genomes, cohesin co-localizes with CCCTC binding factor (CTCF), zinc finger implicated multiple regulatory events. At imprinted IGF2-H19 locus, CTCF plays an role organizing allele-specific higher-order chromatin conformation and functions as...
The molecular regulation of zygotic genome activation (ZGA) in mammals remains an exciting area research. Primed mouse embryonic stem cells contain a rare subset “2C-like” that are epigenetically and transcriptionally similar to the two-cell embryo thus represent vitro approximation for studying ZGA transcription regulation. Recently, factor Dux, expressed minor wave ZGA, was described activate many downstream transcripts. However, it unknown what upstream maternal factors initiate either...
DNA methylation is a repressive epigenetic modification that essential for development, exemplified by the embryonic and perinatal lethality observed in mice lacking de novo methyltransferases (DNMTs). Here we characterise role DNMT3A, 3B 3L gene regulation development of mouse placenta. We find each DNMT establishes unique aspects placental methylome through targeting to distinct chromatin features. Loss Dnmt3b results de-repression germline genes trophoblast lineages impaired formation...
Long noncoding RNAs are implicated in a number of regulatory functions eukaryotic genomes. The paternally expressed long RNA (ncRNA) Kcnq1ot1 regulates epigenetic gene silencing an imprinted cluster cis over distance 400 kb the mouse embryo, whereas silenced region extends 780 placenta. Gene by involves repressive histone modifications, including H3K9me2 and H3K27me3, which partly brought about G9a Ezh2 methyltransferases. Here, we show that is transcribed polymerase II, unspliced,...
The unfolded protein response of the endoplasmic reticulum (UPRER) is a crucial mediator secretory pathway homeostasis. Expression spliced and active form UPRER transcription factor XBP-1, XBP-1s, in nervous system triggers activation intestine Caenorhabditis elegans (C. elegans) through release secreted signal, leading to increased longevity. We find that expression XBP-1s neurons or worm strikingly improves proteostasis multiple tissues, clearance toxic proteins. To identify mechanisms...
Transcription of protein coding genes is accompanied by recruitment COMPASS to promoter-proximal chromatin, which methylates histone H3 lysine 4 (H3K4) form H3K4me1, H3K4me2 and H3K4me3. Here, we determine the importance in maintaining gene expression across lifespan budding yeast. We find that mutations reduce replicative cause defects almost 500 genes. Although H3K4 methylation reported act primarily repression, particularly yeast, repressive functions are progressively lost with age while...
Germinal centres (GCs) are T follicular helper cell (Tfh)-dependent structures that form in response to vaccination, producing long-lived antibody secreting plasma cells and memory B protect against subsequent infection. With advancing age the GC Tfh declines, resulting impaired humoral immunity. We sought discover what underpins poor ageing whether it is possible correct it. Here, we demonstrate older people aged mice have differentiation upon vaccination. This deficit preceded by...
In C. elegans, expression of the UPRER transcription factor xbp-1s in neurons cell non-autonomously activates intestine, leading to enhanced proteostasis and lifespan. To better understand this signaling pathway, we isolated from animals expressing neuronal for transcriptomic analysis, revealing a striking remodeling transcripts involved signaling. We then identified molecules required non-autonomous intestinal activation, including biogenic amine tyramine. Expression just two pairs that...
Abstract The transition from naive to primed pluripotency is accompanied by an extensive reorganisation of transcriptional and epigenetic programmes. However, the role enhancers three-dimensional chromatin organisation in coordinating these developmental programmes remains incompletely understood. Here, we generate a high-resolution atlas gene regulatory interactions, profiles transcription factor occupancy human pluripotent stem cells, develop network-graph approach examine at multiple...
The signalling pathways that maintain primed human pluripotent stem cells (hPSCs) have been well characterised, revealing a critical role for TGFβ/Activin/Nodal signalling. In contrast, the requirements of naïve pluripotency not fully established. Here, we demonstrate TGFβ is required to hPSCs. downstream effector proteins – SMAD2/3 bind common sites in and hPSCs, including shared genes. additionally active regulatory regions near Inhibiting hPSCs causes downregulation SMAD2/3-target genes...
Abstract Ten-eleven-translocation (TET) proteins catalyze DNA hydroxylation, playing an important role in demethylation of mammals. Remarkably, although hydroxymethylation levels are high the mouse brain, potential TET adult neurogenesis is unknown. We show here that a non-catalytic action TET3 essentially required for maintenance neural stem cell (NSC) pool subventricular zone (SVZ) niche by preventing premature differentiation NSCs into non-neurogenic astrocytes. This occurs through direct...
3D DNA FISH has become a major tool for analyzing three-dimensional organization of the nucleus, and several variations technique have been published. In this article we describe protocol which optimized robustness, reproducibility, ease use. Brightly fluorescent directly labeled probes are generated by nick-translation with amino-allyldUTP followed chemical coupling dye. is performed using freeze-thaw step cell permeabilization heating simultaneous denaturation probe nuclear DNA. The...
We demonstrate here that the Tet repressor (TetR), a dimeric allosterical regulatory protein, can be converted to fully functional monomer when connected by 29 amino acid linker. TetR-based transregulators are widely used regulate gene expression in eukaryotes. They fused form single-chain (sc) with two TetR moieties and one eukaryotic domain. Sc variants of transactivator transsilencer exhibit same properties as their respective counterparts human cell lines. In particular, reverse 'tet-on'...
ABSTRACT Integral membrane proteins from over 20 ubiquitous families of channels, secondary carriers, and primary active transporters were analyzed for average size differences between homologues the three domains life: Bacteria , Archaea Eucarya . The results showed that while eucaryotic are consistently larger than their bacterial counterparts, archaeal significantly smaller. These proved to be due primarily variations in sizes hydrophilic localized N termini, C or specific loops...
Although somatic homologous pairing is common in Drosophila it not generally observed mammalian cells. However, a number of regions have recently been shown to come into close proximity with their allele, and has proposed that might be involved the establishment or maintenance monoallelic expression. Here, we investigate properties various imprinted non-imprinted mouse tissues ES We find by allele-specific 4C-Seq DNA FISH Kcnq1 region displays frequent but this dependent on demonstrate...
<ns3:p>Background Robust analysis of DNA sequencing data needs to include a set quality control steps ensure that technical bias is kept minimum. A metric easily obtained the frequency each nucleobases for position across all reads. Here, we explore differences in nucleobase compositions various library types produced by standard experimental methodologies. Methods We nearly 3000 publicly available datasets and subjected them Uniform Manifold Approximation Projection (UMAP) dimensionality...
Abstract Background The amount of a particular protein, and not just its presence or absence, frequently determines the outcome developmental process disease progression. These dosage effects can be studied by conditionally expressing such proteins at different levels. With typical gene regulation systems like Tet‐On system, intermediate expression levels obtained varying effector concentration. However, this strategy is limited to situations in which these concentrations precisely...
ABSTRACT Gene duplication events can drive evolution by providing genetic material for new gene functions, and they create opportunities diverse developmental strategies to emerge between species. To study the contribution of duplicated genes human early development, we examined function NANOGP1, a tandem duplicate transcription factor NANOG. We found that NANOGP1 NANOG have overlapping but distinct expression profiles, with high restricted epiblast cells naïve-state pluripotent stem cells....
BioTechniquesVol. 37, No. 4 BenchmarksOpen AccessTetracycline derivatives: alternative effectors for Tet transregulatorsChristel Krueger, Klaus Pfleiderer, Wolfgang Hillen & Christian BerensChristel KruegerFriedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany, PfleidererFriedrich-Alexander-Universität HillenFriedrich-Alexander-Universität Germany Berens*Address correspondence to: Berens, Lehrstuhl für Mikrobiologie, Friedrich-Alexander-Universität Staudtstr. 5, 91058 Germany....