ArticleScience advances2023
De novo human brain enhancers created by single-nucleotide mutations.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Genomic language model for predicting enhancers and their allele-specific activity in the human genome.Bioinformatics (Oxford, England) · 2026Article
- Emergence Biases in Molecular Evolution.Genome biology and evolution · 2026Review
- Regulatory risk loci link disrupted androgen response to the pathophysiology of polycystic ovary syndrome.Journal of the Endocrine Society · 2026Article
- Article
- Rare regulatory mutations disrupt mesenchymal molecular programs driving endocardial cushion formation in bicuspid aortic valve.Nature communications · 2026Article
- The evolution of gene regulation in mammalian cerebellum development.Science (New York, N.Y.) · 2026Article
- Non-coding genetic variants underlying higher prostate cancer risk in men of African ancestry.Nature communications · 2025Article
- Programming human cell type-specific gene expression via an atlas of AI-designed enhancers.bioRxiv : the preprint server for biology · 2025Article
- Active regulatory elements recruit cohesin to establish cell specific chromatin domains.Scientific reports · 2025Article
- Regulatory Plasticity of the Human Genome.Molecular biology and evolution · 2025Article
- The combinatorial binding syntax of transcription factors in forebrain-specific enhancers.Biology open · 2025Article
- Novelty versus innovation of gene regulatory elements in human evolution and disease.Current opinion in genetics & development · 2025Review
- GATA4 binding to the Sox9 enhancer mXYSRa/Enh13 is critical for testis differentiation in mouse.Communications biology · 2025Article
- How our brains are built: emerging approaches to understand human-specific features.Current opinion in genetics & development · 2024Review
- Massively parallel approaches for characterizing noncoding functional variation in human evolution.Current opinion in genetics & development · 2024Review
- A scalable, high-throughput neural development platform identifies shared impact of ASD genes on cell fate and differentiation.bioRxiv : the preprint server for biology · 2024Article
- Conserved transcriptional regulation by BRN1 and BRN2 in neocortical progenitors drives mammalian neural specification and neocortical expansion.Nature communications · 2024Article
- CpG island turnover events predict evolutionary changes in enhancer activity.Genome biology · 2024Article
- Using a comprehensive atlas and predictive models to reveal the complexity and evolution of brain-active regulatory elements.Science advances · 2024Article
- ChromDL: a next-generation regulatory DNA classifier.Bioinformatics (Oxford, England) · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Advanced human cognition is attributed to increased neocortex size and complexity, but the underlying evolutionary and regulatory mechanisms are largely unknown. Using human and macaque embryonic neocortical H3K27ac data coupled with a deep learning model of enhancers, we identified ~4000 enhancer gains in humans, which, per our model, can often be attributed to single-nucleotide essential mutations. Our analyses suggest that functional gains in embryonic brain development are associated with de novo enhancers whose putative target genes exhibit increased expression in progenitor cells and interneurons and partake in critical neural developmental processes. Essential mutations alter enhancer activity through altered binding of key transcription factors (TFs) of embryonic neocortex, including ISL1, POU3F2, PITX1/2, and several SOX TFs, and are associated with central nervous system disorders. Overall, our results suggest that essential mutations lead to gain of embryonic neocortex enhancers, which orchestrate expression of genes involved in critical developmental processes associated with human cognition.
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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.