- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Fractal and DNA sequence analysis
- Epigenetics and DNA Methylation
- Chromosomal and Genetic Variations
- DNA and Nucleic Acid Chemistry
- Protein Structure and Dynamics
- Machine Learning in Bioinformatics
- DNA Repair Mechanisms
- HIV Research and Treatment
- Bacterial Genetics and Biotechnology
- Micro and Nano Robotics
- HIV/AIDS drug development and treatment
- Microfluidic and Bio-sensing Technologies
- Gene expression and cancer classification
- Plant Molecular Biology Research
- Cytomegalovirus and herpesvirus research
- Genetics, Aging, and Longevity in Model Organisms
- Gene Regulatory Network Analysis
- Genomics and Phylogenetic Studies
- Bacteriophages and microbial interactions
- Electrostatics and Colloid Interactions
- Genomic variations and chromosomal abnormalities
- Bacterial biofilms and quorum sensing
École Normale Supérieure de Lyon
2016-2025
Centre National de la Recherche Scientifique
2016-2025
Laboratoire de Physique de l'ENS de Lyon
2013-2025
Université Claude Bernard Lyon 1
2010-2023
Laboratoire de Biologie et Modélisation de la Cellule
2010
Laboratoire de Physique des 2 Infinis Irène Joliot-Curie
2007-2009
Centre de Génétique Moléculaire
2002-2009
Institut Jacques Monod
2008
Sorbonne Université
2008
Laboratoire de Statistique Théorique et Appliquée
2006-2007
Abstract Genomes of eukaryotes are partitioned into domains functionally distinct chromatin states. These stably inherited across many cell generations and can be remodeled in response to developmental external cues, hence contributing the robustness plasticity expression patterns phenotypes. Remarkably, recent studies indicate that these 1D epigenomic tend fold 3D topologically associated forming specialized nuclear compartments. However, general mechanisms behind such compartmentalization...
To understand the role of extensive senescence-associated 3D genome reorganization, we generated genome-wide chromatin interaction maps, epigenome, replication-timing, whole-genome bisulfite sequencing, and gene expression profiles from cells entering replicative senescence (RS) or upon oncogene-induced (OIS). We identify heterochromatin domains (SAHDs). Differential intra- versus inter-SAHD interactions lead to formation foci (SAHFs) in OIS but not RS. This OIS-specific configuration brings...
We use the "wavelet transform microscope" to carry out a comparative statistical analysis of DNA bending profiles and corresponding texts. In three kingdoms, one reveals on both signals characteristic scale 100-200 bp that separates two different regimes power-law correlations (PLC). small-scale regime, PLC are observed in eukaryotic, double-strand viral, archaeal genomes, which contrasts with their total absence genomes eubacteria viruses. This strongly suggests related mechanisms...
Nucleosome positioning plays an essential role in cellular processes by modulating accessibility of DNA to proteins. Here, using only sequence-dependent flexibility and intrinsic curvature, we predict the nucleosome occupancy along genomes Saccharomyces cerevisiae Drosophila melanogaster demonstrate predictive power universality our model through its correlation with experimentally determined data. In yeast promoter regions, computed average closely superimposes experimental data, exhibiting...
Recent progresses of genome-wide chromatin conformation capture techniques have shown that the genome is segmented into hierarchically organized spatial compartments. However, whether this non-random 3D organization only reflects or indeed contributes—and how—to regulation function remain to be elucidated. The observation in many species domains correlate strongly with 1D epigenomic information along suggests a dynamic coupling between and epigenetic regulation. Here, we posit chromosome...
The spatial organization of the genome plays a crucial role in regulation gene expression. Recent experimental techniques like Hi-C have emphasized segmentation genomes into interaction compartments that constitute conserved functional domains participating maintenance proper cell identity. Here, we propose novel method, IC-Finder, to identify (IC) from maps. IC-Finder is based on hierarchical clustering approach adapted account for polymeric nature chromatin. Based benchmark realistic...
Abstract DNA folding and dynamics along with major nuclear functions are determined by chromosome structural properties, which remain, thus far, elusive in vivo. Here, we combine polymer modeling single particle tracking experiments to determine the physico-chemical parameters of chromatin vitro living yeast. We find that motion reconstituted fibers can be recapitulated Rouse model using mechanical nucleosome arrays deduced from simulations. Conversely, report shows some inconsistencies...
In higher eukaryotes, replication program specification in different cell types remains to be fully understood. We show for seven human lines that about half of the genome is divided domains display a characteristic U-shaped timing profile with early initiation zones at borders and late centers. Significant overlap observed between U-domains also germline exhibiting N-shaped nucleotide compositional skew. From demonstration average fork polarity directly reflected by both skew derivative...
Establishment of stable HIV-1 infection requires the efficient integration retroviral genome into host DNA. The molecular mechanism underlying control this process by chromatin structure has not yet been elucidated. We show here that stably associated nucleosomes strongly inhibit in vitro two viral-end decreasing accessibility DNA to integrase. Remodeling chromatinized template SWI/SNF complex, whose INI1 major component interacts with IN, restores and redirects full-site nucleosome region....
The orientation of the circular motion most swimming E. coli at a solid surface is shown to be (i) reversed by supplementing medium with alginate and (ii) restored rendering glass positively charged. Given slip promotion polymer suppression its anchoring on surface, observations are interpreted boundary. This points out bacterial as probe solid/fluid boundary condition.
Numerous studies of chromatin structure showed that nucleosome free regions (NFRs) located at 5′ gene ends contribute to transcription initiation regulation. Here, we determine the role intragenic on expression We show that, along Saccharomyces cerevisiae genes, nucleosomes are highly organized following two types architecture depend only distance between NFRs and 3′ ends. In first type, this constrains in vivo positioning n regularly a “crystal-like” array. second is such corresponding...
Transcription implies recruitment of RNA polymerase II and transcription factors (TFs) by DNA melting near start site (TSS). Combining atomic force microscopy computer modeling, we investigate the structural dynamical properties IL2RA promoter identify an intrinsically negative supercoil in PRRII region (containing Elf-1 HMGA1 binding sites), located upstream a curved encompassing TSS. Conformational changes, evidenced time-lapse studies, result progressive positioning curvature apex towards...
The adjustment of X-linked gene expression to the X chromosome copy number (dosage compensation [DC]) has been widely studied as a model chromosome-wide regulation. In Caenorhabditis elegans , DC is achieved by twofold down-regulation from both Xs in hermaphrodites. We show that males, single interacts with nuclear pore proteins, while hermaphrodites, complex (DCC) impairs this interaction and alters localization. Our results put forward structural which X-specific sequences locate...
Retroviral integration depends on the interaction between intasomes, host chromatin and cellular targeting cofactors as LEDGF/p75 or BET proteins. Previous studies indicated that retroviral integrase, by itself, may play a role in local site selection within nucleosomal target DNA. We focused our study this association analyzing intrinsic properties of various intasomes to functionally accommodate different structures lack other cofactors.Using vitro conditions allowing efficient catalysis...
Nucleosomes are fundamental units of chromatin in which a length genomic DNA is wrapped around histone octamer spool left-handed superhelix. Large-scale nucleosome maps show wide distribution wrapping lengths, some cases tens base pairs (bp) shorter than the 147 bp canonical observed crystal structures. Here, we develop thermodynamic model that assumes constant free energy cost unwrapping nucleosomal bp. Our also incorporates linker DNA—short segments between neighboring nucleosomes imposed...
Although significant progress has been made on our understanding of DNA replication and spatial chromosome organization in eukaryotes, how they both interplay remains elusive. In particular, from the local structure two diverging sister-forks to higher-level machinery into nuclear domains, mechanistic details chromatin duplication 3D space remain debated. this study, we use a computational model Saccharomyces cerevisiae genome explore influences folding. By integrating realistic description...
Recent genome-wide nucleosome mappings along with bioinformatics studies have confirmed that the DNA sequence plays a more important role in collective organization of nucleosomes vivo than previously thought. Yet living cells, this also results from action various external factors like DNA-binding proteins and chromatin remodelers. To decipher code for intrinsic organization, there is thus need vitro experiments to bridge gap between computational models preferences occupancy data. Here we...