A5080923553- Gene Regulatory Network Analysis
- Genomics and Chromatin Dynamics
- Diffusion and Search Dynamics
- RNA and protein synthesis mechanisms
- Evolution and Genetic Dynamics
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Bacterial Genetics and Biotechnology
- Cell Image Analysis Techniques
- Microtubule and mitosis dynamics
- Protein Degradation and Inhibitors
- Renal and related cancers
- African history and culture analysis
- Bacteriophages and microbial interactions
- Fibroblast Growth Factor Research
- Connective Tissue Growth Factor Research
- Tardigrade Biology and Ecology
- African Studies and Geopolitics
- Reproductive Biology and Fertility
- Genetics, Aging, and Longevity in Model Organisms
- bioluminescence and chemiluminescence research
- Plant Molecular Biology Research
- Ubiquitin and proteasome pathways
- Advanced Proteomics Techniques and Applications
- Chromosomal and Genetic Variations
Institut Pasteur
2020-2023
Princeton University
2018-2023
Université Paris Cité
2023
Centre National de la Recherche Scientifique
2023
Biologie du Développement et Cellules Souches
2023
École Polytechnique Fédérale de Lausanne
2013-2018
SIB Swiss Institute of Bioinformatics
2013
Chromosomes in the eukaryotic nucleus are highly compacted. However, for many functional processes, including transcription initiation, pairwise motion of distal chromosomal elements such as enhancers and promoters is essential necessitates dynamic fluidity. Here, we used a live-imaging assay to simultaneously measure positions pairs their transcriptional output while systematically varying genomic separation between these two DNA loci. Our analysis reveals coexistence compact globular...
Many mammalian genes are transcribed during short bursts of variable frequencies and sizes that substantially contribute to cell-to-cell variability. However, which molecular mechanisms determine bursting properties remains unclear. To probe putative mechanisms, we combined temporal analysis transcription along the circadian cycle with multiple genomic reporter integrations, using both short-lived luciferase live microscopy single-molecule RNA-FISH. Using Bmal1 promoter as our model,...
Significance Recent single-cell studies showed that gene transcription in mammals is fundamentally stochastic, occurring short and intense transcriptional bursts. However, less known on how bursting modulated upon stimulation. Here, we monitor the response of a single allele endogenous connective tissue growth factor gene, encoding secreted protein involved wound healing to shear stress, two different physiological stimuli cells. Analysis using stochastic modeling shows both cause acute...
Article27 July 2015Open Access Structure of silent transcription intervals and noise characteristics mammalian genes Benjamin Zoller The Institute Bioengineering, School Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland Search for more papers by this author Damien Nicolas Nacho Molina Felix Naef Corresponding Author Information Zoller1, Nicolas1, Molina1 1 1The *Corresponding author. Tel: +41 21 693 16 21; E-mail: [email protected] Molecular Systems Biology...
Models of transcriptional regulation that assume equilibrium binding transcription factors have been less successful at predicting gene expression from sequence in eukaryotes than bacteria. This could be due to the non-equilibrium nature eukaryotic regulation. Unfortunately, space possible mechanisms is vast and predominantly uninteresting. The key question therefore how this can navigated efficiently, focus on models are biologically relevant. In review, we advocate for normative role...
Significance Simple biophysical models successfully describe bacterial regulatory code, by predicting gene expression from DNA sequences that bind specialized proteins. Analogous simple fail in multicellular organisms, where proteins very transiently, yet, nevertheless, effect precise control over expression. To date, the more general, “nonequilibrium” have proven difficult to analyze and connect data. Here, we reduce this complexity theoretically, constructing nonequilibrium which perform...
Chromosomes in the eukaryotic nucleus are highly compacted. However, for many functional processes, including transcription initiation, 3D pair-wise motion of distal chromosomal elements, such as enhancers and promoters, is essential necessitates dynamic fluidity. Therefore, interplay chromosome organization dynamics crucial gene regulation. Here, we use a live imaging assay to simultaneously measure positions pairs promoters their transcriptional output developing fly embryo while...
Transcription commonly occurs in bursts, with alternating productive (ON) and quiescent (OFF) periods, governing mRNA production rates. Yet, how transcription is regulated through bursting dynamics remains unresolved. In this study, we conduct real-time measurements of endogenous transcriptional single-mRNA sensitivity. Leveraging the diverse activities early fly embryos, uncover stringent relationships between parameters. Specifically, find that durations ON OFF periods are linked....
In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to expression levels that is compatible with in vivo and vitro bio-physical measurements. Such concordance has not been achieved for enhancer function eukaryotes. equilibrium models, it difficult reconcile the reported short transcription factor (TF) residence times on DNA high specificity regulation. non-equilibrium progress due an explosion number parameters. Here, we...
In early development, regulation of transcription results in precisely positioned and highly reproducible expression patterns that specify cellular identities. How transcription, a fundamentally noisy molecular process, is regulated to achieve reliable embryonic patterning remains unclear. particular, it unknown how gene-specific mechanisms affect kinetic rates whether there are common, global features govern these across genetic network. Here, we measure nascent transcriptional activity the...
In mammals, transcription was observed to occur predominantly in bursts, resulting from short and intense periods of gene interspersed by longer silent periods. order elucidate the causes consequences discontinuous we further extended a probabilistic computational framework model single-cell time-lapse recording luminescent reporter based on stochastic expression models that describe basic processes activation, transcription, translation, degradation mRNA proteins. Motivated recent finding...
Models of transcriptional regulation that assume equilibrium binding transcription factors have been very successful at predicting gene expression from sequence in bacteria. However, analogous models do not perform as well eukaryotes, most likely due to the largely out-of-equilibrium nature eukaryotic regulatory processes. These processes come with unavoidable energy expenditure molecular level support precise, reliable, or fast responses could correspond evolutionarily optimized strategies....