Biology subjects

Louafi, N.

Publications and source records attributed to Louafi, N..

3 recordsLinked to original sources

bioRxiv2025

Loop extrusion creates rare, long-lived encounters underlying enhancer-promoter communication

Enhancers regulate transcription from distal genomic positions, but how their spatial encounters with promoters drive activation remains unclear. Using polymer simulations and high-resolution live-cell microscopy, we identify rare but long-lived chromatin encounters arising from cohesin-mediated loop extrusion. These events occur when cohesin loads near the midpoint between two loci and extrudes them through a defined spatial radius, producing encounter durations that exceed those of random collisions. We show that such encounters explain observed nonlinear relationships between contact probability and transcription, and accurately predict transcriptional changes upon perturbation of cohesin or its cofactors. Our findings support a time-gated model of distal enhancer-promoter communication in which only rare, long-lived and mostly extrusion-driven encounters are productive, offering a unifying framework for how chromosome dynamics control transcription in single cells.

molecular biology↗

bioRxiv2025

NIPBL dosage shapes genome folding by tuning the rate of cohesin loop extrusion

Genome folding is not static, but emerges from dynamic processes that control transcription, replication, recombination, and repair. DNA loop extrusion by cohesin is central to genome organization, yet it remains unclear how cells can tune extrusion kinetics to achieve precise and functional chromosome folding patterns. Here we discover extrusion rate acts as a tunable biophysical parameter in cells, quantitatively dialed by the respective dosage of the cohesin cofactors NIPBL and PDS5. Modulation of extrusion rate can offset changes in cohesin lifetime to buffer steady-state chromosome structure and transcriptional states, even in the face of abnormal extrusion dynamics. These findings provide a long-sought mechanistic basis for the genetic interactions between cohesin cofactors and the molecular origin of haploinsufficiency in cohesinopathies, such as Cornelia de Lange syndrome.

molecular biology↗

bioRxiv2023

Phase separation and molecular ordering of the prion-like domain of the thermosensory protein EARLY FLOWERING 3

Liquid-liquid phase separation (LLPS) is an important mechanism enabling the dynamic compartmentalisation of macromolecules, including complex polymers such as proteins and nucleic acids, and occurs as a function of the physicochemical environment. In the model plant, Arabidopsis thaliana, LLPS by the protein EARLY FLOWERING3 (ELF3) occurs in a temperature sensitive manner and controls thermoresponsive growth. ELF3 contains a largely unstructured prion-like domain (PrLD) that acts as a driver of LLPS in vivo and in vitro. The PrLD contains a poly-glutamine (polyQ) tract, whose length varies across natural Arabidopsis accessions. Here, we use a combination of biochemical, biophysical and structural techniques to investigate the dilute and condensed phases of the ELF3 PrLD with varying polyQ lengths. We demonstrate that the dilute phase of the ELF3 PrLD forms a monodisperse higher order oligomer that does not depend on the presence of the polyQ sequence. This species undergoes LLPS in a pH and temperature-sensitive manner and the polyQ region of the protein tunes the initial stages of phase separation. The liquid phase rapidly undergoes aging and forms a hydrogel as shown by fluorescence and atomic force microscopies. Furthermore, we demonstrate that the hydrogel assumes a semi-ordered structure as determined by small angle X-ray scattering, electron microscopy and X-ray diffraction. These experiments demonstrate a rich structural landscape for a PrLD protein and provide a framework to describe the structural and biophysical properties of biomolecular condensates.

biophysics↗