ArticleeLife2022
A test of the pioneer factor hypothesis using ectopic liver gene activation.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 68 citations in OpenAlex.
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- Genome-wide rotational and translational phasing of nucleosomes with human transcription factors.Molecular cell · 2026Article
- Molecular determinants of AR-enhancer interaction and cistrome reprogramming in prostate cancer progression.Endocrine-related cancer · 2026Review
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- Cohesin Facilitates Nucleosome Invasion by Transcription Factors.bioRxiv : the preprint server for biology · 2025Article
- The transcriptomics of phenotypic nonspecificity in Drosophila melanogaster.G3 (Bethesda, Md.) · 2025Article
- DNA bendability regulates transcription factor binding to nucleosomes.Nature structural & molecular biology · 2025Article
- Proximal Tubule Cells Contribute to the Thin Descending Limb of the Loop of Henle during Mouse Kidney Development.Journal of the American Society of Nephrology : JASN · 2025Article
- Coregulators determine androgen receptor activity in prostate cancer.Bioscience reports · 2025Review
- Time-varying stimuli that prolong IKK activation promote nuclear remodeling and mechanistic switching of NF-κB dynamics.Nature communications · 2025Article
- Defining transcription factor nucleosome binding with Pioneer-seq.PLoS genetics · 2025Article
- An automated ATAC-seq method reveals sequence determinants of transcription factor dose response in the open chromatin.bioRxiv : the preprint server for biology · 2025Article
- Altered cofactor recruitment and nucleosome dynamics underlie bisphenol A's impact on ERα-mediated transcriptional bursting.iScience · 2025Article
- The maternal-to-zygotic transition: reprogramming of the cytoplasm and nucleus.Nature reviews. Genetics · 2025Review
- Chromatin enables precise and scalable gene regulation with factors of limited specificity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- EnhancerNet: a predictive model of cell identity dynamics through enhancer selection.Development (Cambridge, England) · 2024Article
- The yin and yang of pioneer transcription factors: Dual roles in repression and activation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The pioneer factor hypothesis (PFH) states that pioneer factors (PFs) are a subclass of transcription factors (TFs) that bind to and open inaccessible sites and then recruit non-pioneer factors (non-PFs) that activate batteries of silent genes. The PFH predicts that ectopic gene activation requires the sequential activity of qualitatively different TFs. We tested the PFH by expressing the endodermal PF FOXA1 and non-PF HNF4A in K562 lymphoblast cells. While co-expression of FOXA1 and HNF4A activated a burst of endoderm-specific gene expression, we found no evidence for a functional distinction between these two TFs. When expressed independently, both TFs bound and opened inaccessible sites, activated endodermal genes, and 'pioneered' for each other, although FOXA1 required fewer copies of its motif for binding. A subset of targets required both TFs, but the predominant mode of action at these targets did not conform to the sequential activity predicted by the PFH. From these results, we hypothesize an alternative to the PFH where 'pioneer activity' depends not on categorically different TFs but rather on the affinity of interaction between TF and DNA.
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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.