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Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs [ChIP-nexus]

GSE306103 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2025/11/13 Platform GPL19057
Summary
Low-affinity transcription factor motifs are an important element of the cis-regulatory code, yet they cannot be mapped by local sequence scanning without knowledge of the sequence context in which they are functional. Here we leverage sequence-to-profile models of chromatin accessibility and binding in mouse embryonic stem cells to reliably map low-affinity motifs across the genome and deduce the mechanisms by which they become functional. We show that low-affinity motifs are used by pioneer transcription factors and that their effect is disproportionately enhanced by intra-nucleosomal cooperativity with stronger pioneer motifs. By exploring the underlying nucleosome-mediated mechanism with a kinetic model, we discover that pioneer cooperativity, and not low-affinity motifs per se, renders enhancers more responsive to changes in TF concentrations by increasing their regulatory potential. These results show that low-affinity motifs can be accurately mapped and suggest that their inherently strong cooperativity is an important property of developmental enhancers.
Published in
Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs
Weilert M, Brennan KJ, Dalal K et al. · bioRxiv : the preprint server for biology 2025 · PMID 41332771 · doi:10.1101/2025.11.18.685822
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Also filed as BioProject PRJNA1309133 and SRA study SRP610491. Searching any of these in the dataset finder brings you back here.

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