ArticlePLoS genetics2016
A Hox Transcription Factor Collective Binds a Highly Conserved Distal-less cis-Regulatory Module to Generate Robust Transcriptional Outcomes.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
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- Decoding enhancer complexity with machine learning and high-throughput discovery.Genome biology · 2023Review
- A Drosophila Su(H) model of Adams-Oliver Syndrome reveals cofactor titration as a mechanism underlying developmental defects.PLoS genetics · 2022Article
- Thermodynamics-based modeling reveals regulatory effects of indirect transcription factor-DNA binding.iScience · 2022Article
- The wing imaginal disc.Genetics · 2022Article
- Butterfly eyespots evolved via cooption of an ancestral gene-regulatory network that also patterns antennae, legs, and wings.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Cell-type-specific Hox regulatory strategies orchestrate tissue identity.Current biology : CB · 2021Article
- Transcriptional enhancers and their communication with gene promoters.Cellular and molecular life sciences : CMLS · 2021Review
- Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor.PLoS genetics · 2021Article
- Mechanisms of stearoyl CoA desaturase inhibitor sensitivity and acquired resistance in cancer.Science advances · 2021Article
- Mechanisms Underlying Hox-Mediated Transcriptional Outcomes.Frontiers in cell and developmental biology · 2021Review
- Conserved Gsx2/Ind homeodomain monomer versus homodimer DNA binding defines regulatory outcomes in flies and mice.Genes & development · 2021Article
- Gli3 utilizes Hand2 to synergistically regulate tissue-specific transcriptional networks.eLife · 2020Article
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- Physical interactions between Gsx2 and Ascl1 balance progenitor expansion versus neurogenesis in the mouse lateral ganglionic eminence.Development (Cambridge, England) · 2020Article
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- Homotypic cooperativity and collective binding are determinants of bHLH specificity and function.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
cis-regulatory modules (CRMs) generate precise expression patterns by integrating numerous transcription factors (TFs). Surprisingly, CRMs that control essential gene patterns can differ greatly in conservation, suggesting distinct constraints on TF binding sites. Here, we show that a highly conserved Distal-less regulatory element (DCRE) that controls gene expression in leg precursor cells recruits multiple Hox, Extradenticle (Exd) and Homothorax (Hth) complexes to mediate dual outputs: thoracic activation and abdominal repression. Using reporter assays, we found that abdominal repression is particularly robust, as neither individual binding site mutations nor a DNA binding deficient Hth protein abolished cooperative DNA binding and in vivo repression. Moreover, a re-engineered DCRE containing a distinct configuration of Hox, Exd, and Hth sites also mediated abdominal Hox repression. However, the re-engineered DCRE failed to perform additional segment-specific functions such as thoracic activation. These findings are consistent with two emerging concepts in gene regulation: First, the abdominal Hox/Exd/Hth factors utilize protein-protein and protein-DNA interactions to form repression complexes on flexible combinations of sites, consistent with the TF collective model of CRM organization. Second, the conserved DCRE mediates multiple cell-type specific outputs, consistent with recent findings that pleiotropic CRMs are associated with conserved TF binding and added evolutionary constraints.
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