ArticlePLoS genetics2013
Clustering of tissue-specific sub-TADs accompanies the regulation of HoxA genes in developing limbs.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
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Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 190 citations in OpenAlex.
- Discovery of common and rare genetic risk variants for colorectal cancer.Nature genetics · 2019Pooled it
- Loss of multilevel 3D genome organization during breast cancer progression.Genome research · 2026Article
- Evolutionary pathway and genetic mechanisms of fin-to-limb transition in vertebrates.Frontiers in cell and developmental biology · 2026Review
- Article
- CWL-Based Analysis Pipeline for Hi-C Data: From FASTQ Files to Matrices.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Topologically associating domains of chromatin on single-cell Hi-C data: a survey of bioinformatic tools and applications in the light of artificial intelligence.Frontiers in genetics · 2025Review
- Evidence for Fgf and Wnt regulation ofFrontiers in cell and developmental biology · 2025Article
- Mutations of PDS5 genes enhance TAD-like domain formation Arabidopsis thaliana.Nature communications · 2024Article
- A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival.Nature communications · 2024Article
- Article
- Three-dimensional chromatin reorganization regulates B cell development during ageing.Nature cell biology · 2024Article
- A comprehensive benchmarking with interpretation and operational guidance for the hierarchy of topologically associating domains.Nature communications · 2024Article
- Boundary stacking interactions enable cross-TAD enhancer-promoter communication during limb development.Nature genetics · 2024Article
- The 3D Genome in Brain Development: An Exploration of Molecular Mechanisms and Experimental Methods.Neuroscience insights · 2024Review
- Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning.Nature communications · 2023Article
- DeDoc2 Identifies and Characterizes the Hierarchy and Dynamics of Chromatin TAD-Like Domains in the Single Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest.Nature communications · 2023Article
- Shared retinoic acid responsive enhancers coordinately regulate nascent transcription of Hoxb coding and non-coding RNAs in the developing mouse neural tube.Development (Cambridge, England) · 2023Article
- Loop stacking organizes genome folding from TADs to chromosomes.Molecular cell · 2023Article
- Disruption of polyhomeotic polymerization decreases nucleosome occupancy and alters genome accessibility.Life science alliance · 2023Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
HoxA genes exhibit central roles during development and causal mutations have been found in several human syndromes including limb malformation. Despite their importance, information on how these genes are regulated is lacking. Here, we report on the first identification of bona fide transcriptional enhancers controlling HoxA genes in developing limbs and show that these enhancers are grouped into distinct topological domains at the sub-megabase scale (sub-TADs). We provide evidence that target genes and regulatory elements physically interact with each other through contacts between sub-TADs rather than by the formation of discreet "DNA loops". Interestingly, there is no obvious relationship between the functional domains of the enhancers within the limb and how they are partitioned among the topological domains, suggesting that sub-TAD formation does not rely on enhancer activity. Moreover, we show that suppressing the transcriptional activity of enhancers does not abrogate their contacts with HoxA genes. Based on these data, we propose a model whereby chromatin architecture defines the functional landscapes of enhancers. From an evolutionary standpoint, our data points to the convergent evolution of HoxA and HoxD regulation in the fin-to-limb transition, one of the major morphological innovations in vertebrates.
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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.