A5064283272- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Bacteriophages and microbial interactions
- Chromosomal and Genetic Variations
- Cancer-related gene regulation
- RNA Research and Splicing
- Animal Genetics and Reproduction
- Parasitic Diseases Research and Treatment
- Advanced biosensing and bioanalysis techniques
- Insect symbiosis and bacterial influences
- Pluripotent Stem Cells Research
- Parasite Biology and Host Interactions
- Bioinformatics and Genomic Networks
- Genomics and Rare Diseases
- DNA and Nucleic Acid Chemistry
- Congenital heart defects research
- RNA Interference and Gene Delivery
- Gene expression and cancer classification
New England Biolabs (United States)
2016-2025
New England Biolabs (China)
2021-2024
Heidelberg University
2008-2019
Steno Diabetes Centers
2019
European Molecular Biology Organization
2007-2015
European Molecular Biology Laboratory
2007-2008
European Bioinformatics Institute
2003-2008
Centre National de la Recherche Scientifique
2006-2007
European Molecular Biology Laboratory
2007
Wellcome Trust
2005-2007
Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart distribution of gene along mouse genome, using hundreds insertions sensor. found enhancers distribute their broad regions and not gene-centric manner, defining domains. Remarkably, domains correlate strongly with recently described TADs, which partition...
Proneural genes such as Ascl1 are known to promote cell cycle exit and neuronal differentiation when expressed in neural progenitor cells. The mechanisms by which proneural activate neurogenesis--and, particular, the that they regulate--however, mostly unknown. We performed a genome-wide characterization of transcriptional targets embryonic brain stem cultures location analysis expression profiling embryos overexpressing or mutant for Ascl1. wide range molecular cellular functions...
Mutations in somatic cells generate a heterogeneous genomic population and may result serious medical conditions. Although cancer is typically associated with variations, advances DNA sequencing indicate that cell-specific variants affect number of phenotypes pathologies. Here, we show mutagenic damage accounts for the majority erroneous identification low to moderate (1 5%) frequency. More important, found signatures most data sets widely used resources, including 1000 Genomes Project The...
The majority of neural stem cells (NSCs) in the adult brain are quiescent, and this fraction increases with aging. Although signaling pathways that promote NSC quiescence have been identified, transcriptional mechanisms involved mostly unknown, largely due to lack a cell culture model. In study, we first demonstrate cultures (NS cells) exposed BMP4 acquire cellular characteristics quiescent cells. We then use epigenomic profiling identify enhancers associated NS state. Motif enrichment...
The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how interacts with chromatin landscape regulate when promoting differentiation. We find that binding occurs mostly at distal enhancers is associated activation transcription. Surprisingly, accessibility its sites neural stem/progenitor cells remains largely unchanged throughout...
The initiating nucleotide found at the 5' end of primary transcripts has a distinctive triphosphorylated that distinguishes these from all other RNA species. Recognizing this distinction is key to deconvoluting transcriptome plethora processed confound analysis transcriptome. currently available methods do not use targeted enrichment for 5'end transcripts, but rather attempt deplete non-targeted RNA.We developed method, Cappable-seq, directly enriching and enabling determination...
Current methods for genome-wide analysis of gene expression require fragmentation original transcripts into small fragments short-read sequencing. In bacteria, the resulting fragmented information hides operon complexity. Additionally, in vivo processing confounds accurate identification 5' and 3' ends operons. Here we develop a methodology called SMRT-Cappable-seq that combines isolation un-fragmented primary with single-molecule long read Applied to E. coli, this technology results an...
The predominant methodology for DNA methylation analysis relies on the chemical deamination by sodium bisulfite of unmodified cytosine to uracil permit differential readout methylated cytosines. Bisulfite treatment damages DNA, leading fragmentation and loss long-range information. To overcome this limitation bisulfite-treated we applied a new enzymatic approach, termed methyl-seq (EM-seq), sequencing technologies. Our methodology, named long-read modification (LR-EM-seq), preserves...
Most organisms possess circadian clocks that are able to anticipate the day/night cycle and reset or "entrained" by ambient light. In zebrafish, many organs even cultured cell lines directly light responsive, allowing for direct entrainment of clock Here, we have characterized induced gene transcription in zebrafish at several organizational levels. Larvae, heart organ cultures were exposed 1- 3-hour pulses, changes expression compared with controls kept dark. We identified 117 regulated...
Programmed cell death (PCD) during neuronal development and disease has been shown to require de novo RNA synthesis. However, the time course regulation of target genes is poorly understood. By using a brain-biased array over 7,500 cDNAs, we profiled this gene expression component PCD in cerebellar granule neurons challenged separately by potassium withdrawal, combined serum kainic acid administration. We found that hundreds were significantly regulated discreet waves including known whose...
Evolutionary innovation relies partially on changes in gene regulation. While a growing body of evidence demonstrates that such is generated by functional or translocation regulatory elements via mobile genetic elements, the de novo generation enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated. Here we show for genesis vertebrates. For this, took advantage massive loss following last whole genome duplication teleosts systematically...
The gene regulatory network (GRN) that supports neural stem cell (NS cell) self-renewal has so far been poorly characterized. Knowledge of the central transcription factors (TFs), noncoding regions they bind to, and genes whose expression modulate will be crucial in unlocking full therapeutic potential these cells. Here, we use DNase-seq combination with analysis histone modifications to identify multiple classes epigenetically functionally distinct cis-regulatory elements (CREs). Through...
Abstract Methylation patterns in bacteria can be used to study restriction–modification or other defense systems with novel properties. While m4C and m6A methylation are well characterized mainly through PacBio sequencing, the landscape of m5C is under-characterized. To bridge this gap, we performed RIMS-seq2 (rapid identification methyltransferase specificity sequencing) on microbiomes composed resolved assemblies distinct genomes proximity ligation. This high-throughput approach enables...
The central nervous system of persons with Down syndrome presents cytoarchitectural abnormalities that likely result from gene-dosage effects affecting the expression key developmental genes. To test this hypothesis, we have investigated transcriptome cerebellum Ts1Cje mouse model during postnatal development using microarrays and quantitative PCR (qPCR). Genes present in three copies were consistently overexpressed, a mean ratio relative to euploid 1.52 as determined by qPCR. Out 63...
Determination of eukaryotic transcription start sites (TSSs) has been based on methods that require the cap structure at 5' end transcripts derived from Pol II RNA polymerase. Consequently, these do not reveal TSSs other polymerases also play critical roles in various cell functions. To address this limitation, we developed ReCappable-seq, which comprehensively identifies TSS for both and non-Pol single-nucleotide resolution. The method relies specific enzymatic exchange m7G caps...
The SARS-CoV-2 virus has a complex transcriptome characterised by multiple, nested subgenomic RNAsused to express structural and accessory proteins. Long-read sequencing technologies such as nanopore direct RNA can recover full-length transcripts, greatly simplifying the assembly of structurally RNAs. However, these techniques do not detect 5' cap, thus preventing reliable identification quantification full-length, coding transcript models. Here we used Nanopore ReCappable Sequencing...
The intracellular endosymbiotic proteobacteria Wolbachia have evolved across the phyla nematoda and arthropoda. In phylogeny, supergroup F is only clade known so far with members from both arthropod filarial nematode hosts therefore can provide unique insights into their evolution biology. this study, 4 new genomes been assembled using a metagenomic assembly binning approach, wMoz wMpe human parasites Mansonella ozzardi perstans, wOcae wMoviF blue mason bee Osmia caerulescens sheep ked...
The filarial parasites Mansonella ozzardi and perstans , causative agents of mansonellosis, infect hundreds millions people worldwide, yet remain among the most understudied human pathogens. M. is highly prevalent in Latin American countries Caribbean Islands, while predominantly found sub-Saharan Africa as well a few areas South America. In addition to differences their geographical distribution, two are transmitted by different insect vectors, exhibit responses commonly used anthelminthic...
Abstract To understand the aetiology and phenotypic severity of Down syndrome, we searched for transcriptional signatures in a substructure brain (cerebellum) during post‐natal development segmental trisomy 16 model, Ts1Cje mouse. The goal this study was to investigate effects on changes gene expression across time. primary gene‐dosage effect triplicated genes (∼1.5) observed at birth [post‐natal day 0 (P0)], P15 P30. About 5% non‐triplicated were significantly differentially expressed...
So far, the computational identification of transcription factor binding sites is hampered by complexity vertebrate genomes. Here we present an in silico procedure to predict target a complex genomes using its site. In first step sequence, comparison closely related identifies conserved cis-regulatory regions (phylogenetic footprinting). Subsequently, more remote are introduced into identify highly and therefore putatively functional filtering). When applied site atonal homolog 5 (Ath5 or...
Abstract Bacteria respond to their environment by regulating mRNA synthesis, often altering the genomic sites at which RNA polymerase initiates transcription. Here, we investigate genome-wide changes in transcription start site (TSS) usage Clostridium phytofermentans , a model bacterium for fermentation of lignocellulosic biomass. We quantify expression nearly 10,000 TSS single base resolution Capp-Switch sequencing, combines capture synthetically capped 5′ fragments with template-switching...