ArticlePLoS genetics2019
Low affinity binding sites in an activating CRM mediate negative autoregulation of the Drosophila Hox gene Ultrabithorax.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Continuous negative autoregulation fine-tunes dosage-sensitive transcription factor expression to maintain post-mitotic neuron identity.bioRxiv : the preprint server for biology · 2026Article
- Bipartite DNA binding domain of transcription factor BCL11B binds clustered short DNA sequence motifs.bioRxiv : the preprint server for biology · 2026Article
- Multimeric transcription factor BCL11A utilizes two zinc-finger tandem arrays to bind clustered short sequence motifs.Nature communications · 2025Article
- Probing the role of the protonation state of a minor groove-linker histidine in Exd-Hox-DNA binding.Biophysical journal · 2024Article
- Single-nucleotide variants within heart enhancers increase binding affinity and disrupt heart development.Developmental cell · 2023Article
- The activity of engrailed imaginal disc enhancers is modulated epigenetically by chromatin and autoregulation.PLoS genetics · 2023Article
- DNA selection by the master transcription factor PU.1.Cell reports · 2023Article
- Characterisation of the role and regulation ofFrontiers in cell and developmental biology · 2023Article
- Maintenance of neurotransmitter identity by Hox proteins through a homeostatic mechanism.Nature communications · 2022Article
- Evolution of stickleback spines through independent cis-regulatory changes at HOXDB.Nature ecology & evolution · 2022Article
- A synthetic synthesis to explore animal evolution and development.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
- Different transcriptional responses by the CRISPRa system in distinct types of heterochromatin in Drosophila melanogaster.Scientific reports · 2022Article
- SpyChIP identifies cell type-specific transcription factor occupancy from complex tissues.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Fluorescent labeling of genomic loci inCell reports methods · 2022Article
- Micromanagement ofJournal of developmental biology · 2022Review
- Both Binding Strength and Evolutionary Accessibility Affect the Population Frequency of Transcription Factor Binding Sequences in Arabidopsis thaliana.Genome biology and evolution · 2021Article
- Cell-type-specific Hox regulatory strategies orchestrate tissue identity.Current biology : CB · 2021Article
- Hox dosage contributes to flight appendage morphology in Drosophila.Nature communications · 2021Article
- Developmental Robustness: The Haltere Case inFrontiers in cell and developmental biology · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Specification of cell identity and the proper functioning of a mature cell depend on precise regulation of gene expression. Both binary ON/OFF regulation of transcription, as well as more fine-tuned control of transcription levels in the ON state, are required to define cell types. The Drosophila melanogaster Hox gene, Ultrabithorax (Ubx), exhibits both of these modes of control during development. While ON/OFF regulation is needed to specify the fate of the developing wing (Ubx OFF) and haltere (Ubx ON), the levels of Ubx within the haltere differ between compartments along the proximal-distal axis. Here, we identify and molecularly dissect the novel contribution of a previously identified Ubx cis-regulatory module (CRM), anterobithorax (abx), to a negative auto-regulatory loop that decreases Ubx expression in the proximal compartment of the haltere as compared to the distal compartment. We find that Ubx, in complex with the known Hox cofactors, Homothorax (Hth) and Extradenticle (Exd), acts through low-affinity Ubx-Exd binding sites to reduce the levels of Ubx transcription in the proximal compartment. Importantly, we also reveal that Ubx-Exd-binding site mutations sufficient to result in de-repression of abx activity in a transgenic context are not sufficient to de-repress Ubx expression when mutated at the endogenous locus, suggesting the presence of multiple mechanisms through which Ubx-mediated repression occurs. Our results underscore the complementary nature of CRM analysis through transgenic reporter assays and genome modification of the endogenous locus; but, they also highlight the increasing need to understand gene regulation within the native context to capture the potential input of multiple genomic elements on gene control.
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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.