Biomedical subjects

Arnaud R Krebs

Publications and source records attributed to Arnaud R Krebs.

3 recordsLinked to original sources

PubMed2026

A practical guide to studying genome function using single-molecule genomics.

Single-molecule genomics (SMG) has transformed our ability to study the mechanisms that regulate the genome by enabling profiling of the activity of regulatory factors on individual DNA molecules genome-wide. SMG is able to quantify molecular heterogeneity and the co-occurrence of regulatory events, including epigenetic modifications, transcription factor binding and chromatin organization on single DNA molecules. SMG reveals dynamics of chromatin interactions that cannot be measured by conventional genomics assays. Therefore, SMG offers a unique platform to study how regulatory events combine to control genome activity. In this Expert Recommendation article, we provide a practical guide for adopting SMG and outline best practices.

Journal Article↗

PubMed2026

Molecular co-accessibility identifies coordinated regulation between distant cis-regulatory elements.

In metazoans, gene expression is typically regulated by a cis-regulatory landscape (CRL) composed of a promoter and multiple enhancers. How these cis-regulatory elements (CREs) coordinate their function across large genomic distances remains unclear. For example, is the simultaneous activation of multiple enhancers required to promote transcription? Here, we combined single-molecule footprinting with long-read sequencing to quantify how often chromatin accessibility and transcription factor binding co-occur across entire CRLs in the Drosophila genome. Analysis of thousands of individual DNA molecules at each locus revealed that CREs form a specific network with shared single-molecule chromatin accessibility profiles. Co-accessibility is not limited to adjacent CREs and is frequently observed between CREs brought into proximity by chromatin looping. Co-accessible CREs exhibit strong coordination in their cell-type-specific accessibility, linking enhancer activity with transcriptional activation. Our data uncover dependencies between CREs genome-wide and suggest that coordinated enhancer activation is a widespread mechanism regulating gene expression.

Animals↗

PubMed2025

FootprintCharter: unsupervised detection and quantification of footprints in single molecule footprinting data.

SUMMARY: Single molecule footprinting profiles the heterogeneity of TF occupancy at cis-regulatory elements across cell populations at unprecedented resolution. The single molecule nature of the data in principle allows for observing the footprint of individual transcription factors and nucleosomes. However, we currently lack algorithms to quantify these occupancy patterns of chromatin binding factors in an automated way and without prior assumptions on their genomic location. Here we present FootprintCharter, an unsupervised tool to detect and quantify footprints for transcription factors (TFs) and nucleosomes from single molecule footprinting data. After detection, TF footprints can be labeled with orthogonal motif annotations provided by the user. FootprintCharter allows for the quantification of complex molecular states such as positioning of unphased nucleosomes and combinatorial co-binding of multiple TFs. AVAILABILITY AND IMPLEMENTATION: FootprintCharter is freely available on Bioconductor with version 2.2.0 of https://bioconductor.org/packages/SingleMoleculeFootprinting through the functions FootprintCharter, PlotFootprints, and Plot_FootprintCharter_SM.

Transcription Factors↗