ArticleDevelopmental cell2016
The Shh Topological Domain Facilitates the Action of Remote Enhancers by Reducing the Effects of Genomic Distances.
Article in Developmental cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed, 244 citations in OpenAlex.
- De novo structural variants in autism spectrum disorder disrupt distal regulatory interactions of neuronal genes.Genome research · 2026Article
- Mechanisms and functional implications of long-range enhancer-dependent gene regulation.Nature genetics · 2026Review
- A Genotype-Phenotype Analysis of Four Chinese Children Carrying Distinct Pathogenic Variants in theGenes · 2026Article
- Down-regulation of Shh in the hair follicles of mice during chemotherapy-induced hair loss is mediated by the JAK/STAT1 signaling pathway.FEBS open bio · 2026Article
- Convergence of external and internal stressors on a stress-responsive enhancer of theProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Synergy between regulatory elements can render cohesin dispensable for distal enhancer function.Science (New York, N.Y.) · 2026Article
- Temporal constraints on enhancer usage shape the regulation of limb gene transcription.Nature communications · 2026Article
- Discovering the complete enhancer map of human herpesviruses using a natural language processing model.Nature communications · 2025Article
- Disentangling the architectural and non-architectural functions of CTCF and cohesin in gene regulation.Nature genetics · 2025Article
- Positional programs in early murine facial development and their role in human facial shape variability.Nature communications · 2025Article
- Is enhancer-driven gene regulation all wrapped up?Nature reviews. Genetics · 2025Article
- Functional maps of a genomic locus reveal confinement of an enhancer by its target gene.Science (New York, N.Y.) · 2025Article
- Bystander activation across a TAD boundary supports a cohesin-dependent transcription cluster model for enhancer function.Genes & development · 2025Article
- RNA-binding proteins mediate the maturation of chromatin topology during differentiation.Nature cell biology · 2025Article
- Reactivation of developmentally silenced globin genes through forced linear recruitment of remote enhancers.Blood · 2025Article
- Genomic locus of lncRNA-Gm26793 forms an inter-chromosomal interaction with Cubn to ensure proper stem cell differentiation in vitro and in vivo.Cell discovery · 2025Article
- Transposable elements as genome regulators in normal and malignant haematopoiesis.Blood cancer journal · 2025Review
- PBX1 and PBX3 transcription factors regulate SHH expression in the Frontonasal Ectodermal Zone through complementary mechanisms.PLoS genetics · 2025Article
- Genetic factors mediating long-range enhancer-promoter communication in mammalian development.Current opinion in genetics & development · 2025Review
- Long-range regulation of transcription scales with genomic distance in a gene-specific manner.Molecular cell · 2025Article
83 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene expression often requires interaction between promoters and distant enhancers, which occur within the context of highly organized topologically associating domains (TADs). Using a series of engineered chromosomal rearrangements at the Shh locus, we carried out an extensive fine-scale characterization of the factors that govern the long-range regulatory interactions controlling Shh expression. We show that Shh enhancers act pervasively, yet not uniformly, throughout the TAD. Importantly, changing intra-TAD distances had no impact on Shh expression. In contrast, inversions disrupting the TAD altered global folding of the region and prevented regulatory contacts in a distance-dependent manner. Our data indicate that the Shh TAD promotes distance-independent contacts between distant regions that would otherwise interact only sporadically, enabling functional communication between them. In large genomes where genomic distances per se can limit regulatory interactions, this function of TADs could be as essential for gene expression as the formation of insulated neighborhoods.
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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.