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Accueil > Équipes > Chromatine et Régulation de la Pathogénie bactérienne > Dynamique de la chromatine et expression des gènes

Chromatin dynamics and gene expression

DNA carries two information types : the linear genetic code and the equally important 3D structural code determining the chromosome configuration, both “inscribed” in the primary sequence organization of the DNA and thus interdependent. A major objective of the CRP team is to characterize the relation between the chromosome configuration and the genome expression pattern, using the phytopathogenic bacterium Dickeya dadantii as a model. Investigation tools include transcriptomics, chromosome manipulation, computational and biophysical modeling.

Experimental investigation of the Dickeya dadantii transcriptome

We develop extensive investigation of the Dickeya dadantii transcriptome in various conditions : successive environmental stresses encountered during plant infection, supercoiling relaxation by antibiotic gyrase inhibitors, mutations in nucleoid-associated proteins involved in chromosome structuring… The objective is to get a detailed, quantitative and mechanistic view of transcriptional regulation at the genomic scale. Recent investigations include the genome-wide mapping of transcription start sites.

Functional macrodomains in the Dickeya genome
The genome is divided into macrodomains with distinctive architectural and functional properties

Multiscale investigation of spatial expression domains on the chromosome

Gene expression is spatially organized on the chromosome at different lengthscales : as an example, during plant infection, large spatial clusters of genes are transiently expressed together, which do not share any transcription factor but are rather located in a common chromosomal domain. The objective is to quantitatively understand the mechanisms underpinning these domains, as they emerge from the interplay of supercoiling-coupled transcription at the kilobase-scale with a time-dependent redistribution of architectural proteins.

Spatial organization of Dickeya dadantii gene expression during plant infection
Each circle represents the bacterial chromosome, colors range from blue (repressed genes) to red (activated). Outer to inner circle : successive environmental stresses encountered by the bacteria during plant infection

Computational modeling of DNA mechanical deformations and structural transitions in the chromosome

The team develops a computational biophysics approach to analyze the role of DNA sequence-dependent physical properties in the chromosome structure and regulation.
Most architectural and regulatory proteins induce substantial mechanical deformations in the double helix (Figure), the cost of which is modulated by the sequence through DNA structure and elasticity. We develop efficient softwares based on coarse-grained (nanoscale) models of DNA to analyze these modulations at the genomic scale, compare these distributions with observations, and estimate their effect on gene regulation. We also use thermodynamic models of DNA to estimate how torsional stress distributes along the chromosome and promotes transient DNA denaturation events required for transcription. See the website of our bioinformatics group.

DNA mechanical distorsions involved in regulatory protein binding
Architectural proteins have a dual role in shaping the chromosome and in regulating gene expression. The physical code encoded in the DNA sequence plays a role in directing regulatory proteins to their target sequences.