ArticleNature communications2022
Context-dependent enhancer function revealed by targeted inter-TAD relocation.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Temporal constraints on enhancer usage shape the regulation of limb gene transcription.Nature communications · 2026Article
- Article
- Exploring the roles of conserved context-dependent cis-regulatory elements (cdCREs) in multicellularity, human health and disease.The FEBS journal · 2025Review
- Structural variants in the 3D genome as drivers of disease.Nature reviews. Genetics · 2025Review
- Genetic coupling of enhancer activity and connectivity in gene expression control.Nature communications · 2025Article
- Biology of Hox Genes: Questions and Technological Challenges.Methods in molecular biology (Clifton, N.J.) · 2025Review
- CTCF-dependent insulation ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mutations of PDS5 genes enhance TAD-like domain formation Arabidopsis thaliana.Nature communications · 2024Article
- CRISPR screening uncovers a long-range enhancer for ONECUT1 in pancreatic differentiation and links a diabetes risk variant.Cell reports · 2024Article
- Genomic context sensitizes regulatory elements to genetic disruption.Molecular cell · 2024Article
- Genomic context sensitizes regulatory elements to genetic disruption.bioRxiv : the preprint server for biology · 2024Article
- eQTL mapping in fetal-like pancreatic progenitor cells reveals early developmental insights into diabetes risk.Nature communications · 2023Article
- Three-dimensional genome structure and function.MedComm · 2023Review
- Article
- Function and Evolution of the Loop Extrusion Machinery in Animals.International journal of molecular sciences · 2023Review
- Shared cis-regulatory modules control expression of the tandem paralogs midline and H15 in the follicular epithelium.Development (Cambridge, England) · 2022Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The expression of some genes depends on large, adjacent regions of the genome that contain multiple enhancers. These regulatory landscapes frequently align with Topologically Associating Domains (TADs), where they integrate the function of multiple similar enhancers to produce a global, TAD-specific regulation. We asked if an individual enhancer could overcome the influence of one of these landscapes, to drive gene transcription. To test this, we transferred an enhancer from its native location, into a nearby TAD with a related yet different functional specificity. We used the biphasic regulation of Hoxd genes during limb development as a paradigm. These genes are first activated in proximal limb cells by enhancers located in one TAD, which is then silenced when the neighboring TAD activates its enhancers in distal limb cells. We transferred a distal limb enhancer into the proximal limb TAD and found that its new context suppresses its normal distal specificity, even though it is bound by HOX13 transcription factors, which are responsible for the distal activity. This activity can be rescued only when a large portion of the surrounding environment is removed. These results indicate that, at least in some cases, the functioning of enhancer elements is subordinated to the host chromatin context, which can exert a dominant control over its activity.
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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.