ArticleNature structural & molecular biology2025
Mesoscale chromatin confinement facilitates target search of pioneer transcription factors in live cells.
Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Nucleosomes and IDRs suppress promiscuous GCN4 binding on minichromosomes.Nature structural & molecular biology · 2026Article
- Pioneer-factor activity requires stable chromatin occupancy mediated by both sequence-specific binding and disordered protein domains.Science advances · 2026Article
- Single-molecule localization and diffusivity microscopy reveals dynamic biomolecular organization in living cells.Nature methods · 2026Article
- Increased Telomere Mobility in Progeria is Restored by Isoprenylcysteine Carboxyl Methyltransferase Inhibition.bioRxiv : the preprint server for biology · 2026Article
- Electrostatic properties of disordered regions control transcription factor search and pioneer activity.Nature communications · 2026Article
- Genome integrity relies on rapid recycling of DNA Pol III in bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pre-established ATF4 occupancy and chromatin organization instruct selective transcription activation during integrated stress response.Nature communications · 2025Article
- Structural insights into the recognition of native nucleosomes by pioneer transcription factors.Current opinion in structural biology · 2025Review
- Rethinking chromatin accessibility: from compaction to dynamic interactions.Current opinion in genetics & development · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pioneer transcription factors (PTFs) possess the unique capability to access closed chromatin regions and initiate cell fate changes, yet the underlying mechanisms remain elusive. Here, we characterized the single-molecule dynamics of PTFs targeting chromatin in living cells, revealing a notable 'confined target search' mechanism. PTFs such as FOXA1, FOXA2, SOX2, OCT4 and KLF4 sampled chromatin more frequently than non-PTF MYC, alternating between fast free diffusion in the nucleus and slower confined diffusion within mesoscale zones. Super-resolved microscopy showed closed chromatin organized as mesoscale nucleosome-dense domains, confining FOXA2 diffusion locally and enriching its binding. We pinpointed specific histone-interacting disordered regions, distinct from DNA-binding domains, crucial for confined target search kinetics and pioneer activity within closed chromatin. Fusion to other factors enhanced pioneer activity. Kinetic simulations suggested that transient confinement could increase target association rate by shortening search time and binding repeatedly. Our findings illuminate how PTFs recognize and exploit closed chromatin organization to access targets, revealing a pivotal aspect of gene regulation.
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Registered trials
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