ArticleDevelopmental biology2013
Pitx1 broadly associates with limb enhancers and is enriched on hindlimb cis-regulatory elements.
Article in Developmental biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 64 citations in OpenAlex.
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- Developmental and transcriptional programs that define the initiation of the forelimb.Development (Cambridge, England) · 2026Article
- Unraveling the Clinical and Genetic Landscape of Talipes Equinovarus (Clubfoot).Molecular syndromology · 2026Review
- Developmental and transcriptional programs that define the initiation of the forelimb.bioRxiv : the preprint server for biology · 2025Article
- Evolution of cetacean-specific conserved non-coding elements suggests their role in the limb changes during secondary aquatic adaptation.BMC biology · 2025Article
- Liebenberg syndrome severity arises from variations in Pitx1 locus topology and proportion of ectopically transcribing cells.Nature communications · 2025Article
- Functional evidence supports the potential role of Tbx4-HLEA in the hindlimb degeneration of cetaceans.EvoDevo · 2025Article
- PITX1 as a grading, prognostic and tumor-infiltrating immune cells marker for chondrosarcoma: a public database-based immunoassay and tissue sample analysis.Frontiers in oncology · 2025Article
- Developmental regulation of conserved non-coding element evolution provides insights into limb loss in squamates.Science China. Life sciences · 2023Article
- Identification of candidate enhancers controlling the transcriptome during the formation of interphalangeal joints.Scientific reports · 2022Article
- Cell-specific alterations in Pitx1 regulatory landscape activation caused by the loss of a single enhancer.Nature communications · 2021Article
- (Non)Parallel developmental mechanisms in vertebrate appendage reduction and loss.Ecology and evolution · 2021Review
- Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin.Nature communications · 2021Article
- Tbx4 function during hindlimb development reveals a mechanism that explains the origins of proximal limb defects.Development (Cambridge, England) · 2021Article
- The transcription factor PITX1 drives astrocyte differentiation by regulating the SOX9 gene.The Journal of biological chemistry · 2020Article
- Article
- Developmental and Evolutionary Allometry of the Mammalian Limb Skeleton.Integrative and comparative biology · 2019Review
- Pigeon foot feathering reveals conserved limb identity networks.Developmental biology · 2019Article
- Genome Sequencing of the Japanese Eel (Marine drugs · 2019Article
- Silenced PITX1 promotes chemotherapeutic resistance to 5-fluorocytosine and cisplatin in gastric cancer cells.Experimental and therapeutic medicine · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Extensive functional analyses have demonstrated that the pituitary homeodomain transcription factor Pitx1 plays a critical role in specifying hindlimb morphology in vertebrates. However, much less is known regarding the target genes and cis-regulatory elements through which Pitx1 acts. Earlier studies suggested that the hindlimb transcription factors Tbx4, HoxC10, and HoxC11 might be transcriptional targets of Pitx1, but definitive evidence for direct regulatory interactions has been lacking. Using ChIP-Seq on embryonic mouse hindlimbs, we have pinpointed the genome-wide location of Pitx1 binding sites during mouse hindlimb development and identified potential gene targets for Pitx1. We determined that Pitx1 binding is significantly enriched near genes involved in limb morphogenesis, including Tbx4, HoxC10, and HoxC11. Notably, Pitx1 is bound to the previously identified HLEA and HLEB hindlimb enhancers of the Tbx4 gene and to a newly identified Tbx2 hindlimb enhancer. Moreover, Pitx1 binding is significantly enriched on hindlimb relative to forelimb-specific cis-regulatory features that are differentially marked by H3K27ac. However, our analysis revealed that Pitx1 also strongly associates with many functionally verified limb enhancers that exhibit similar levels of activity in the embryonic mesenchyme of forelimbs and hindlimbs. We speculate that Pitx1 influences hindlimb morphology both through the activation of hindlimb-specific enhancers as well as through the hindlimb-specific modulation of enhancers that are active in both sets of limbs.
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