Unstructured transcription factor interactions enable emergent specificity

Transcription factors (TFs) contain intrinsically disordered regions (IDRs) whose role in chromatin binding and nuclear organization is poorly understood. Using proximity-assisted photoactivation (PAPA), a single-molecule sensor capable of detecting protein-protein interactions in living cells, researchers examined how IDRs influence TF behavior. They found that the DNA-binding domain (DBD) of the TF Sp1 alone interacted weakly with chromatin and failed to colocalize with full-length Sp1. An isolated IDR showed only weak affinity for full-length Sp1, but this interaction strengthened when the IDR was fused to various unrelated DBDs. Live imaging in Drosophila polytene chromosomes further demonstrated that an IDR could grant sharp, locus-specific binding to an otherwise non-selective DBD. The results suggest that TF binding specificity on chromatin is an emergent property arising when collections of weak, disordered interactions are organized through transient DNA contacts.

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Importance of elephants for dung beetle biodiversity and ecosystem functions

Ecologists have long predicted that losing highly connected species will cause cascading extinctions, but direct evidence has been rare. This study examined how elephants fit into the broader web of interactions between dung beetles and large herbivores across East Africa. Network analysis placed elephants at the center of this system, and computer simulations predicted that their extinction would cause outsized declines in dung beetle diversity. A 15-year field experiment confirmed this: removing elephants significantly reduced dung beetle abundance, species diversity, and related ecosystem functions such as nutrient cycling and seed dispersal, while excluding smaller ungulates made little additional difference. Surveys of nearby areas where livestock had replaced elephants reinforced these experimental findings. The results provide strong empirical support for the keystone species concept, demonstrating that large, extinction-vulnerable animals sustain entire communities of dependent organisms and the ecological services they provide.

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Pan-cancer spatial atlas of tertiary lymphoid structures

Tertiary lymphoid structures (TLSs) are immune cell clusters that form within tumors and influence anti-cancer responses, but how their internal organization relates to clinical outcomes across different cancers has been poorly understood. Researchers used spatial transcriptomics across 12 cancer types to build a comprehensive TLS atlas, mapping how these structures mature and reorganize surrounding cell populations. They found that TLS maturation involves coordinated changes in niche cells and creates distance-dependent gradients in tumor gene programs, a finding confirmed through high-dimensional single-cell spatial profiling. To make TLS assessment practical at scale, the team trained an AI model to predict TLS maturation states directly from standard hematoxylin and eosin stained tissue images, validating it across TCGA datasets and independent treatment cohorts. A composite score derived from this maturation framework outperformed existing TLS metrics in stratifying patient outcomes across multiple cancer types and therapeutic contexts.

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