ArticleCell2015
Low affinity binding site clusters confer hox specificity and regulatory robustness.
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 238 papers.
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Who cites it
238 citing papers in PubMed.
- Lentiviral single-cell MPRA of synthetic enhancers reveals motif affinity-based encoding of cell state specificity.Genome biology · 2026Article
- Combinatorial pioneer transcription factor binding reinforces bivalent epigenetic states to preserve lineage fidelity.bioRxiv : the preprint server for biology · 2026Article
- Review
- Multi-scale dissection, compaction and derivatization of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- Distinct mechanisms decommission redundant enhancers to facilitate phenotypic evolution.Science advances · 2026Article
- An inducible system to study the regulatory functions of GSX2 in human lateral ganglionic eminence-like progenitors.Developmental biology · 2026Article
- Sequence-based modeling of low-affinity transcription factor-DNA binding through deep learning.NAR genomics and bioinformatics · 2026Article
- Evolutionary turnover of key amino acids explains conservation of function without conservation of sequence in transcriptional activation domains.PLoS genetics · 2026Article
- Quantitative modulation of a spatial enhancer through the biophysical properties of a transcription factor binding site.Science advances · 2026Article
- Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs.bioRxiv : the preprint server for biology · 2025Article
- Modulating MyoD1 dosage activates alternate cell fate beyond myogenic differentiation.bioRxiv : the preprint server for biology · 2025Article
- Machine Learning-Driven Prediction of Spatiotemporal Dynamics of Active Nuclei DuringInternational journal of molecular sciences · 2025Article
- Article
- Emergence of activation or repression in transcriptional control under a fixed molecular context.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Teamwork of clustered low-affinity κB sites and accessory factors regulates transcriptional strength of NF-κB RelA dimers.Nucleic acids research · 2025Article
- Predicting the DNA binding specificity of transcription factor mutants using family-level biophysically interpretable machine learning.Nucleic acids research · 2025Article
- Bicoid-nucleosome competition sets a concentration threshold for transcription constrained by genome replication.Cell reports · 2025Article
- Short activation domains control chromatin association of transcription factors.bioRxiv : the preprint server for biology · 2025Article
- Genetic effects on chromatin accessibility uncover mechanisms of liver gene regulation and quantitative traits.Genome research · 2025Article
- Article
178 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors.
Funding
Abstract
In animals, Hox transcription factors define regional identity in distinct anatomical domains. How Hox genes encode this specificity is a paradox, because different Hox proteins bind with high affinity in vitro to similar DNA sequences. Here, we demonstrate that the Hox protein Ultrabithorax (Ubx) in complex with its cofactor Extradenticle (Exd) bound specifically to clusters of very low affinity sites in enhancers of the shavenbaby gene of Drosophila. These low affinity sites conferred specificity for Ubx binding in vivo, but multiple clustered sites were required for robust expression when embryos developed in variable environments. Although most individual Ubx binding sites are not evolutionarily conserved, the overall enhancer architecture-clusters of low affinity binding sites-is maintained and required for enhancer function. Natural selection therefore works at the level of the enhancer, requiring a particular density of low affinity Ubx sites to confer both specific and robust expression.
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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.