ArticleNature communications2022
Modeling uniquely human gene regulatory function via targeted humanization of the mouse genome.
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 31 papers.
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Who cites it
31 citing papers in PubMed, 39 citations in OpenAlex.
- The gene-regulatory evolution of the human skeleton.Nature · 2026Article
- A Human Accelerated Region Drives Opposing Heterochronic Changes in Craniofacial and Limb Development.bioRxiv : the preprint server for biology · 2026Article
- ClinASO: An open-source platform for rapid drug discovery of gapmer antisense oligonucleotides.Molecular therapy. Nucleic acids · 2026Article
- Genomic approaches for understanding the evolution of the human brain.Nature neuroscience · 2026Review
- Cross-species prediction reveals chromatin regions with increased accessibility in humans.Science advances · 2026Article
- Species-specific chromatin architecture and neurogenesis mediated by a human enhancer.Cell stem cell · 2026Article
- Complementary constraints in germ and immune cells shape evolution of gene regulation and phenotype.bioRxiv : the preprint server for biology · 2026Article
- In silico genome transplants and the cis-regulatory basis of biodiversity.Trends in genetics : TIG · 2026Review
- Nicheformer: a foundation model for single-cell and spatial omics.Nature methods · 2025Article
- An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility.Science advances · 2025Article
- Decoding DNA sequence-driven evolution of the human brain epigenome at cellular resolution.Nature communications · 2025Article
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- Reconstructing human-specific regulatory functions in model systems.Current opinion in genetics & development · 2024Review
- How our brains are built: emerging approaches to understand human-specific features.Current opinion in genetics & development · 2024Review
- A versatile pipeline to identify convergently lost ancestral conserved fragments associated with convergent evolution of vocal learning.Briefings in bioinformatics · 2024Article
- The Human Accelerated Region HAR202 Controls NPAS3 Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences.Molecular biology and evolution · 2024Article
- Evolutionary Innovations in Conserved Regulatory Elements Associate With Developmental Genes in Mammals.Molecular biology and evolution · 2024Article
- Massively parallel approaches for characterizing noncoding functional variation in human evolution.Current opinion in genetics & development · 2024Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The evolution of uniquely human traits likely entailed changes in developmental gene regulation. Human Accelerated Regions (HARs), which include transcriptional enhancers harboring a significant excess of human-specific sequence changes, are leading candidates for driving gene regulatory modifications in human development. However, insight into whether HARs alter the level, distribution, and timing of endogenous gene expression remains limited. We examined the role of the HAR HACNS1 (HAR2) in human evolution by interrogating its molecular functions in a genetically humanized mouse model. We find that HACNS1 maintains its human-specific enhancer activity in the mouse embryo and modifies expression of Gbx2, which encodes a transcription factor, during limb development. Using single-cell RNA-sequencing, we demonstrate that Gbx2 is upregulated in the limb chondrogenic mesenchyme of HACNS1 homozygous embryos, supporting that HACNS1 alters gene expression in cell types involved in skeletal patterning. Our findings illustrate that humanized mouse models provide mechanistic insight into how HARs modified gene expression in human evolution.
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Registered trials
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.