ArticleNature communications2021
Cell-specific alterations in Pitx1 regulatory landscape activation caused by the loss of a single enhancer.
Article in Nature communications, 2021. 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.
- Temporal constraints on enhancer usage shape the regulation of limb gene transcription.Nature communications · 2026Article
- The dorsal aortic compartment is a developmental source of brown adipose tissue in mice.Nature communications · 2026Article
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- Reporter CRISPR screens decipher cis-regulatory and trans-regulatory principles at the Xist locus.Nature structural & molecular biology · 2025Article
- Liebenberg syndrome severity arises from variations in Pitx1 locus topology and proportion of ectopically transcribing cells.Nature communications · 2025Article
- The transcription factor PITX1 cooperates with super-enhancers to regulate the expression of DUSP4 and inhibit pyroptosis in pulmonary artery smooth muscle cells.Respiratory research · 2025Article
- Single-cell profiling of penta- and tetradactyl mouse limb buds identifies mesenchymal progenitors controlling digit numbers and identities.Nature communications · 2025Article
- A comprehensive study of Z-DNA density and its evolutionary implications in birds.BMC genomics · 2024Article
- A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival.Nature communications · 2024Article
- Pre-hypertrophic chondrogenic enhancer landscape of limb and axial skeleton development.Nature communications · 2024Article
- Sall genes regulate hindlimb initiation in mouse embryos.Genetics · 2024Article
- Boundary stacking interactions enable cross-TAD enhancer-promoter communication during limb development.Nature genetics · 2024Article
- Three-dimensional genome structure and function.MedComm · 2023Review
- Genetic cold cases: lessons from solving complex congenital limb disorders.Genes & development · 2023Review
- Context-dependent enhancer function revealed by targeted inter-TAD relocation.Nature communications · 2022Article
- baredSC: Bayesian approach to retrieve expression distribution of single-cell data.BMC bioinformatics · 2022Article
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Authors and funding
7 authors.
Funding
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Abstract
Developmental genes are frequently controlled by multiple enhancers sharing similar specificities. As a result, deletions of such regulatory elements have often failed to reveal their full function. Here, we use the Pitx1 testbed locus to characterize in detail the regulatory and cellular identity alterations following the deletion of one of its enhancers (Pen). By combining single cell transcriptomics and an in-embryo cell tracing approach, we observe an increased fraction of Pitx1 non/low-expressing cells and a decreased fraction of Pitx1 high-expressing cells. We find that the over-representation of Pitx1 non/low-expressing cells originates from a failure of the Pitx1 locus to coordinate enhancer activities and 3D chromatin changes. This locus mis-activation induces a localized heterochrony and a concurrent loss of irregular connective tissue, eventually leading to a clubfoot phenotype. This data suggests that, in some cases, redundant enhancers may be used to locally enforce a robust activation of their host regulatory landscapes.
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