Biology subjects

Cournac, A.

Publications and source records attributed to Cournac, A..

6 recordsLinked to original sources

bioRxiv2026

A radial map of the budding yeast genome reveals novel organizational principles

The eukaryotic genome is non-randomly organized within the nucleus, with positioning linked to function. Still, genome-wide radial maps are missing for the majority of experimental model systems. We adapted Genomic loci Positioning by Sequencing (GPSeq) to Saccharomyces cerevisiae, enabling high-resolution mapping along the nuclear center-periphery axis. GPSeq confirms known spatial features and shows that peripheral telomeres and centromeres impose long-range constraints extending up to 200 kb, restricting short chromosome arms from the nuclear interior. Telomere repositioning to the nuclear center, either artificially or during quiescence, reorganizes much of the genome through inward movement of sub telomeric regions and compensatory shifts of mid-arm chromatin outward. In quiescence, reduced centromere peripheral localization further alters genome organization. While transcription has a modest impact on radial positioning in all studied conditions, we uncover that in the absence of centromere or telomere constraints, GC-content functionally organizes chromatin in the nucleus. Graphical abstractThe budding yeast genome is spatially organized in a manner highly dependent on the positioning of centromeres (CENs) and telomeres (TELs). Anchoring of these chromosome landmarks constrains the positioning of adjacent chromatin up to 200 kb within the same radial zone. Beyond this range, genome organization is non-random, with processes like transcription and features such as GC- content associated with specific radial positions in the nucleus. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/722996v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1c0a383org.highwire.dtl.DTLVardef@2f1e91org.highwire.dtl.DTLVardef@17ff2ecorg.highwire.dtl.DTLVardef@1257f64_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

Hicberg: Reconstruction of contact signals from repeated elements

In the course of their evolution, genomes can acquire various repeated elements, such as transposons, ribosomal DNA, duplicated genes or tandem repeats. These types of sequences cannot be processed directly by current high-throughput sequencing pipelines, as they generate short reads that cannot be unambiguously localized on reference genomes. We propose an algorithm called Hicberg that uses statistical inference with the computation of probability distributions to precisely reassign the positions of reads from repeated sequences in different paired omics data, such as Hi-C data. We show that Hicberg can generate new insights into the impact of repeated elements on the spatial organisation of genomes. Significance StatementThe genomes of microorganisms can contain various types of repeated sequences: duplicated genes, low-complexity sequences and transposons. The question of their potential impact on the spatial organization of genomes is now wide open. We propose Hicberg, an algorithm capable of reconstructing contact signals from repeated elements. It computes statistical trends on the unambiguous part of the genome and then, by statistical inference, reassigns the position of multi-mapping reads. The complete chromosome contact maps thus reveal new observations on the impact of repeated elements on chromosome architecture. In particular, they suggest the involvement of certain retrotransposons in the positioning of cohesins, the molecular motors behind chromosome loops. Classification: Biophysics and Computational Biology section

genomics↗

bioRxiv2023

Transcription promotes discrete long-range chromatin loops besides organizing cohesin-mediated DNA folding

The multi-layered arrangement of eukaryotic genomes and chromosome spatial organization dynamics are of functional importance for gene expression, DNA replication and segregation. SMC complexes are essential instruments of chromosome folding by carrying out long range intra-chromatid DNA looping. Cohesin, in addition to tether sister chromatids, also ensures dynamic regulation of gene expression in mammals by promoting interaction between distal regulatory elements and promoters whereas transcription affects genome folding in numerous organisms and in multiple ways. Here, we comprehensively dissect the relative contributions of transcription and cohesin complexes, as well as their interplay, on the yeast S. cerevisiae genome organization through DNA borders and loops. Transcription activation specifically induces appearance of DNA borders and loops, independently of SMC complexes, while also directly interfering in addition with cohesin-mediated loop expansion.

genomics↗

bioRxiv2023

Anchoring of parasitic plasmids to inactive regions of eukaryotic chromosomes through nucleosome signal

Natural plasmids are common in prokaryotes but few have been documented in eukaryotes. The natural 2{micro} plasmid present in budding yeast Saccharomyces cerevisiae is one of the most well characterized. This highly stable genetic element coexists with its host for millions of years, efficiently segregating at each cell division through a mechanism that remains poorly understood. Using proximity ligation (Hi-C, Micro-C) to map the contacts between the 2{micro} and yeast chromosomes under dozens of different biological conditions, we found that the plasmid tether preferentially on regions with low transcriptional activity, often corresponding to long inactive genes. Common players in chromosome structure such as members of the structural maintenance of chromosome complexes (SMC) are not involved in these contacts which depend instead on a nucleosomal signal associated with a depletion of RNA Pol II. These contacts are stable throughout the cell cycle, and can be established within minutes. This strategy may involve other types of DNA molecules and species other than S. cerevisiae, as suggested by the binding pattern of the natural plasmid along the silent regions of the chromosomes of Dictyostelium discoideum.

genomics↗

bioRxiv2020

Chromosight: A computer vision program for pattern detection in chromosome contact maps

Chromosomes of all species studied so far display a variety of higher order organizational features such as domains or loops often associated to biological functions and visible on Hi-C contact maps. We developed Chromosight, an algorithm inspired from computer vision that can detect patterns in Hi-C maps. Chromosight has greater sensitivity than existing methods, while being faster and applicable to any type of genomes, including bacteria, viruses, yeasts and mammals. Code and documentation: https://github.com/koszullab/chromosight

bioinformatics↗

bioRxiv2019

A major role for Eco1 in regulating cohesin-mediated mitotic chromosome folding

Understanding how chromatin organizes spatially into chromatid and how sister chromatids are maintained together during mitosis is of fundamental importance in chromosome biology. Cohesin, a member of the Structural Maintenance of Chromosomes (SMC) complex family, holds sister chromatids together 1-3 and promotes long-range intra-chromatid DNA looping 4,5. These cohesin-mediated DNA loops are important for both higher-order mitotic chromatin compaction6,7 and, in some organisms, compartmentalization of chromosomes during interphase into topologically associating domains (TADs) 8,9. Our understanding of the mechanism(s) by which cohesin generates large DNA loops remains incomplete. It involves a combination of molecular partners and active expansion/extrusion of DNA loops. Here we dissect the roles on loop formation of three partners of the cohesin complex: Pds5 10, Wpl1 11 and Eco1 acetylase 12, during yeast mitosis. We identify a new function for Eco1 in negatively regulating cohesin translocase activity, which powers loop extrusion. In the absence of negative regulation, the main barrier to DNA loop expansion appears to be the centromere. Those results provide new insights on the mechanisms regulating cohesin dependent DNA looping.

genetics↗