ArticleThe EMBO journal2023
Pioneer activity distinguishes activating from non-activating SOX2 binding sites.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- dubTAGs enable on-demand stabilization for tunable and reversible control of endogenous protein levels.bioRxiv : the preprint server for biology · 2026Article
- Systematic comparison of estimates of transcription factor activity by ATAC-seq and multiplexed reporter assays.Molecular systems biology · 2026Article
- Cumulative transcription factor binding and p300-mediated histone acetylation drive enhancer activation frequency.Nature genetics · 2026Article
- Positional interpretation of cis-regulatory code and nucleosome organization with deep learning models.Nature communications · 2026Article
- Article
- Cohesin-mediated loop extrusion and enhancer-associated factors additively contribute toGenes & development · 2026Article
- Dual role of ZIC2 during neural induction: from priming transcription factor to enhancer activator.Nucleic acids research · 2026Article
- Electrostatic properties of disordered regions control transcription factor search and pioneer activity.Nature communications · 2026Article
- Synergy between regulatory elements can render cohesin dispensable for distal enhancer function.Science (New York, N.Y.) · 2026Article
- OTX2 controls chromatin accessibility to direct somatic versus germline differentiation.EMBO reports · 2026Article
- Article
- Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs.bioRxiv : the preprint server for biology · 2025Article
- Is Enhancer Function Driven by Protein-Protein Interactions? From Bacteria to Leukemia.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- ZNF143 is a transcriptional regulator of nuclear-encoded mitochondrial genes that acts independently of looping and CTCF.Molecular cell · 2025Article
- Article
- Short circuit: Transcription factor addiction as a growing vulnerability in cancer.Current opinion in structural biology · 2024Review
- Optimized reporters for multiplexed detection of transcription factor activity.bioRxiv : the preprint server for biology · 2024Article
- Exploring the reciprocity between pioneer factors and development.Development (Cambridge, England) · 2024Review
- Structural dynamics in chromatin unraveling by pioneer transcription factors.Biophysical reviews · 2024Review
- Early neural specification of stem cells is mediated by a set of SOX2-dependent neural-associated enhancers.Stem cell reports · 2024Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Genome-wide transcriptional activity involves the binding of many transcription factors (TFs) to thousands of sites in the genome. Pioneer TFs are a class of TFs that maintain open chromatin and allow non-pioneer TFs access to their target sites. Determining which TF binding sites directly drive transcription remains a challenge. Here, we use acute protein depletion of the pioneer TF SOX2 to establish its functionality in maintaining chromatin accessibility. We show that thousands of accessible sites are lost within an hour of protein depletion, indicating rapid turnover of these sites in the absence of the pioneer factor. To understand the relationship with transcription, we performed nascent transcription analysis and found that open chromatin sites that are maintained by SOX2 are highly predictive of gene expression, in contrast to all other SOX2 binding sites. We use CRISPR-Cas9 genome editing in the Klf2 locus to functionally validate a predicted regulatory element. We conclude that the regulatory activity of SOX2 is exerted mainly at sites where it maintains accessibility and that other binding sites are largely dispensable for gene regulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.