Venkiteswaran Pottore, K. | Search bioRxiv

bioRxiv2026

Interactome Specialization Predicts Genome-Wide Binding-Site Degeneracy in Drosophila melanogaster Transcription Factors

Transcription factors (TFs) recognize short, degenerate DNA motifs that occur thousands of times throughout the genome, implying that binding specificity depends not only on DNA sequence but also on cellular context, including selective protein-protein interactions. Here, we tested whether a TFs integration into the physical TF interaction network predicts the degeneracy of its DNA-binding motif. Using 279 Drosophila melanogaster TFs with matched JASPAR position weight matrices, FlyBase expression profiles, and a physical protein interaction network derived from STRING v12.0 using only experimental and curated-database evidence, we quantified each TFs TF-module fraction. We compared it with genome-wide predicted binding-site density across an independently constructed 18 Mb genomic sample.TF module fraction showed a significant positive association with binding-site density (partial r = 0.379, P = 5.6e-11)after controlling for motif information content, network degree, and literature bias. The relationship remained significant after excluding the homeodomain family, adding motif architecture controls, and applying multiple robustness analyses, including family-cluster bootstrapping and outlier-resistant correlation tests. Consistent with these findings, TFs formed a highly interconnected physical interaction network far exceeding degree-matched random expectation. Together, these results support a model in which DNA-recognition specificity and protein-interaction specificity represent complementary components of TF targeting: TFs embedded within TF-rich interaction modules tend to possess more degenerate DNA-binding motifs, whereas broadly acting network-generalist TFs rely on more information-rich sequence recognition. We also identify and correct a motif-length-dependent thresholding artifact that can obscure this relationship in genome-wide motif analyses.

genomics↗

bioRxiv2026

Inferotemporal Cortex Joins the Circuit Before the Code: Non-Serial Inter-Area Synergy in the Macaque Ventral Stream

The ventral visual stream is widely modeled as a serial feedforward hierarchy in which V1, V4, and IT population codes develop sequentially during object recognition. We ask whether a second, concurrent coding mode exists--one organized not by anatomical order but by joint population structure across areas. Using Partial Information Decomposition applied to simultaneous multielectrode spiking recordings across all three areas at millisecond resolution--the first simultaneous three-area spiking PID analysis of the primate ventral stream--in two macaque monkeys viewing 25,000+ natural images, we decompose population coding into serial (unique per area) and synergistic (joint across areas) components at 5 ms resolution across five CNN target representations spanning low-level spatial features to high-level object identity. Three findings replicate across both animals and all five representations. First, synergistic inter-area coupling emerges before IT carries any unique object-related information--a dissociation of 15-65 ms that replicates in direction without exception across both animals--such that the joint population integrates before the apex encodes; moreover, V1-IT synergy persists for over 120 ms after V1s unique information reaches zero. Second, although V1{leftrightarrow}IT and V1{leftrightarrow}V4 coupling emerge simultaneously and rise in parallel, V1{leftrightarrow}IT exhibits stronger peak synergy at mid-to-high-level targets in both animals, suggesting a dominant role for non-serial joint coding. Third, when V1 and V4 are treated as an integrated feedforward block, their synergistic coupling with IT emerges last across all tested conditions--the feedforward foundation is the final component to join the synergistic mode, not the first. Together, these results show that serial and synergistic population codes co-occur in the same recordings, overlap in time, but follow different organizational principles, Providing a new level of nuance in our understanding of the primate ventral stream and introducing concrete constraints for biologically grounded models of vision.

neuroscience↗