Transcription factor clusters as information transfer agents

Rahul Munshi; Jia Ling; Sergey Ryabichko; Eric F Wieschaus; Thomas Gregor

Home/Archive/arXiv

arXiv · 2403.02943

Transcription factor clusters as information transfer agents

Rahul Munshi·Jia Ling·Sergey Ryabichko·Eric F Wieschaus·Thomas Gregor

View original source ↗Read source document ↗Export metadata ↓

Abstract

Deciphering how genes interpret information from the concentration of transcription factors (TFs) within the cell nucleus remains a fundamental question in gene regulation. Recent advancements have unveiled the heterogeneous distribution of TF molecules in the nucleus, posing challenges to the precise decoding of concentration signals. To explore this phenomenon, we employ high-resolution single-cell imaging of a fluorescently tagged TF protein, Bicoid, in living fly embryos. We show that accumulation of Bicoid in submicron clusters preserves the spatial information of the maternal Bicoid gradient, and that cluster intensity, size, and frequency offer remarkably precise spatial cues. We further discover that various known gene targets of Bicoid activation colocalize with clusters and that for the target gene Hunchback, this colocalization is dependent on its enhancer binding affinity. Modeling information transfer through these clusters suggests that clustering offers a more rapid sensing mechanism for global nuclear concentrations than freely diffusing TF molecules detected by simple enhancers.

Explore related subjects

physics.bio-ph

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Rahul Munshi, Jia Ling, Sergey Ryabichko, Eric F Wieschaus, Thomas Gregor. 2024-11-06. Transcription factor clusters as information transfer agents. https://arxiv.org/abs/2403.02943

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Tracking and distinguishing slime mold solutions to traveling salesperson problems through synchronized amplification in the non-equilibrium steady state

The plasmodium of the true slime mold Physarum polycephalum-an ancient, unicellular, aneural organism-serves as a platform for studying the information-processing capacities of active matter. Previous experiments used Physarum's intricate morphological dynamics and photoavoidance in stellate chips to solve $N$-city traveling salesperson problems (TSPs) of up to eight cities, scaling linearly in time with TSP size. Optical feedback controlled by a modified Hopfield network illuminated specific lanes at regular intervals, prompting Physarum to elongate or retract selected branches. When the illumination pattern stabilized in a non-equilibrium steady state, branches bifurcated reproducibly into solution and non-solution groups, with the former exhibiting lower-frequency, higher-amplitude, and more synchronized oscillations than the latter across 41 trials with valid TSP solutions. Physarum's synchronization dynamics efficiently predict 100% of selected solutions by the midpoint of the optical-feedback interval, achieving statistically significant (paired t-test, $p<0.005$) discrimination from alternate tours well before the non-equilibrium steady state. Observed frequency downconversions and synchronized power amplifications scale linearly and quadratically, respectively, for small-to-moderate TSP size, as captured by a toy model of energy redistribution with saturating optical absorption. Tuning these features in native biomolecular chromophore networks may thus improve both the quality and efficiency of TSP solutions from Physarum-based biocomputers, which exploit the effects of organismal-scale coherence.

physics.bio-ph↗

arXiv2026

How do incorrect ligands help detect a correct ligand?

Intrigued by the response of T cell receptors to the presence of a few agonist ligands, we propose a minimal model that can achieve similar performance. The model consists of a small cluster of immobile receptors that bind reversibly to two types (correct/incorrect) of ligands in the environment, with slightly weaker binding strength for the incorrect one. It features binding-state coupling between nearest-neighbor receptors, and receptors in the bound/free states are activated/deactivated by specific enzymes, with rates that allow kinetic proofreading. It is found that, for a range of binding-state coupling strength, incorrect ligands alone cannot activate the receptors, but the binding of merely one correct ligand to a receptor is sufficient to promote the activation of other receptors via induced binding to incorrect ligands. Both response time and signal amplification increase as the receptor binding-state coupling strength increases until it reaches an optimal range to achieve the most rapid and sensitive response. These results suggest a possible mechanism for a speedy and specific response of receptors to very few correct ligands in biological and artificial systems at the subcellular scale.

physics.bio-ph↗

arXiv2026

Coherence in Biological Systems

When does a collection of autonomous cells become a multicellular individual? We propose that coherence provides a physical description of this transition. Coherence is treated as a global property arising when distinguishable constituents admit a physically meaningful collective state-space description. Using the center of mass and an interaction-based construction, we show that such collective states can be defined for classical bodies before dynamics is introduced, with normal modes emerging as a particular dynamical realization. We apply this framework to multicellular organization, where cells retain their identities while their independent individuality is replaced by participation in the organized whole. In \emph{Dictyostelium discoideum}, cAMP-mediated coupling produces population-level collective modes, while starvation provides an experimentally controlled energetic constraint on the transition to multicellularity. The framework yields direct tests through interaction-derived collective eigenstates and the energetic cost of maintaining autonomous versus collective organization. Coherence may thus provide a general physical description of multicellular individuality without requiring microscopic quantum coherence or intrinsic wave character.

physics.bio-ph↗