Transcription factor clusters as information transfer agents

Sci Adv. 2025 Jan 3;11(1):eadp3251. doi: 10.1126/sciadv.adp3251. Epub 2025 Jan 1.

Abstract

Deciphering how genes interpret information from transcription factor (TF) concentrations within the cell nucleus remains a fundamental question in gene regulation. Recent advancements have revealed the heterogeneous distribution of TF molecules, posing challenges to precisely decoding concentration signals. Using high-resolution single-cell imaging of the fluorescently tagged TF Bicoid in living Drosophila embryos, we show that Bicoid accumulation in submicrometer clusters preserves the spatial information of the maternal Bicoid gradient. These clusters provide precise spatial cues through intensity, size, and frequency. We further discover that Bicoid target genes colocalize with these clusters in an enhancer-binding affinity-dependent manner. Our modeling suggests that clustering offers a faster sensing mechanism for global nuclear concentrations than freely diffusing TF molecules detected by simple enhancers.

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian / metabolism
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • Drosophila Proteins
  • Transcription Factors
  • Homeodomain Proteins
  • Trans-Activators
  • bcd protein, Drosophila