Biology subjects

Fourel, G.

Publications and source records attributed to Fourel, G..

3 recordsLinked to original sources

bioRxiv2023

ProA and ProB repeat sequences shape genome organization, and enhancers open domains

Genome organization is partially conserved across cell types, yet its DNA-encoded determinants remain incompletely understood. Here we define ProA and ProB repeat sequences (RepSeqs) as two classes of cis-elements that promote A/euchromatin or B/heterochromatin compartment identity. We show that relative ProA/ProB density predicts Hi-C compartment profiles, indicating that compartmental propensity is largely encoded in sequence composition, and point to specific chromatin-based mechanisms underlying these effects. ProA RepSeqs are predominantly Alu elements, whereas ProB RepSeqs comprise young LINE-1s, selected ERVs, AT-rich microsatellites, and satellite repeats. RepSeqs of more indefinite character, including transcriptional enhancers, can switch between ProA and ProB functions to open or close chromatin domains in a context-dependent manner. In cancer, CpG methylation loss disproportionately impacts ProB RepSeqs, weakening the B compartment and thereby contributing to genome unfolding and cancer cell plasticity.

genetics↗

bioRxiv2023

Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization

Although our understanding of the involvement of heterochromatin architectural factors in shaping nuclear organization is improving, there is still ongoing debate regarding the role of active genes in this process. In this study, we utilize publicly-available Micro-C data from mouse embryonic stem cells to investigate the relationship between gene transcription and 3D gene folding. Our analysis uncovers a nonmonotonic - globally positive - correlation between intragenic contact density and Pol II occupancy, independent of cohesin-based loop extrusion. Through the development of a biophysical model integrating the role of transcription dynamics within a polymer model of chromosome organization, we demonstrate that Pol II-mediated attractive interactions with limited valency between transcribed regions yield quantitative predictions consistent with chromosome-conformation-capture and live-imaging experiments. Our work provides compelling evidence that transcriptional activity shapes the 4D genome through Pol II-mediated micro-compartmentalization.

biophysics↗

bioRxiv2020

Dynamics as a cause for the nanoscale organization of the genome

Chromatin blobs were recently identified by live super-resolution imaging as pervasive, but transient and dynamic structural entities consisting of a few associating nucleosomes. The origin and functional implications of these blobs are, however, unknown. Following these findings, we explore whether causal relationships exist between parameters characterizing the chromatin blob dynamics and structure, by adapting a framework for spatio-temporal Granger-causality inference. Our analysis reveals that chromatin dynamics is a key determinant of both blob area and local density. However, such causality can only be demonstrated in small areas (10 - 20%) of the nucleus, highlighting that chromatin dynamics and structure at the nanoscale is dominated by stochasticity. Pixels for which the inter-blob distance can be effectively demonstrated to depend on chromatin dynamics appears as clump in the nucleus, and display both a higher blob density and higher local dynamics as compared with the rest of the nucleus. Furthermore, we show that the theory of active semiflexible polymers can be invoked to provide potential mechanisms leading to the organization of chromatin into blobs. Based on active motion-inducing effectors, this framework qualitatively recapitulates experimental observations and predicts that chromatin blobs might be formed stochastically by a collapse of local polymer segments consisting of a few nucleosomes. Our results represent a first step towards elucidating the mechanisms that govern the dynamic and stochastic organization of chromatin in a cell nucleus.

biophysics↗