ArticleGenome biology2022
A quantitative metric of pioneer activity reveals that HNF4A has stronger in vivo pioneer activity than FOXA1.
Article in Genome biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 32 citations in OpenAlex.
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- Functional annotation of non-coding variants identifies a novel enhancer with activity in neural crest cell-derived lineages.Research square · 2026Article
- Designing synthetic regulatory elements using the generative AI framework DNA-Diffusion.Nature genetics · 2026Article
- Genetic variation shapes the chromatin accessibility landscape and transcriptional responses in mouse adipose tissue.PLoS genetics · 2026Article
- Review
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- Neocortical neurogenesis: a proneural gene perspective.The FEBS journal · 2025Review
- 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
- Chromatin-dependent motif syntax defines differentiation trajectories.Molecular cell · 2025Article
- H3K4me2 distinguishes a distinct class of enhancers during the maternal-to-zygotic transition.PLoS biology · 2025Article
- HNF4A promotes tumor progression in gastric cancer by transcriptional activation of KIF2C.Clinical and experimental medicine · 2025Article
- Are complex traits underpinned by polygenic molecular traits? A reflection on the complexity of gene expression.Plant & cell physiology · 2025Review
- Rise and SINE: roles of transcription factors and retrotransposons in zygotic genome activation.Nature reviews. Molecular cell biology · 2025Article
- Single cell spatial biology over developmental time can decipher pediatric brain pathologies.Neurobiology of disease · 2024Review
- Genetic variation is a key determinant of chromatin accessibility and drives differences in the regulatory landscape of C57BL/6J and 129S1/SvImJ mice.Nucleic acids research · 2024Article
- FOXA1 and FOXA2: the regulatory mechanisms and therapeutic implications in cancer.Cell death discovery · 2024Review
- Protein-intrinsic properties and context-dependent effects regulate pioneer factor binding and function.Nature structural & molecular biology · 2024Article
Corrections and comments
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2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWe and others have suggested that pioneer activity - a transcription factor's (TF's) ability to bind and open inaccessible loci - is not a qualitative trait limited to a select class of pioneer TFs. We hypothesize that most TFs display pioneering activity that depends on the TF concentration and the motif content at their target loci.
resultsHere, we present a quantitative in vivo measure of pioneer activity that captures the relative difference in a TF's ability to bind accessible versus inaccessible DNA. The metric is based on experiments that use CUT&Tag to measure the binding of doxycycline-inducible TFs. For each location across the genome, we determine the concentration of doxycycline required for a TF to reach half-maximal occupancy; lower concentrations reflect higher affinity. We propose that the relative difference in a TF's affinity between ATAC-seq labeled accessible and inaccessible binding sites is a measure of its pioneer activity. We estimate binding affinities at tens of thousands of genomic loci for the endodermal TFs FOXA1 and HNF4A and show that HNF4A has stronger pioneer activity than FOXA1. We show that both FOXA1 and HNF4A display higher binding affinity at inaccessible sites with more copies of their respective motifs. The quantitative analysis of binding suggests different modes of binding for FOXA1, including an anti-cooperative mode of binding at certain accessible loci.
conclusionsOur results suggest that relative binding affinities are reasonable measures of pioneer activity and support the model wherein most TFs have some degree of context-dependent pioneer activity.
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