ArticleCell2018
Ultraconserved Enhancers Are Required for Normal Development.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed.
- In silico genome transplants and the cis-regulatory basis of biodiversity.Trends in genetics : TIG · 2026Review
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- A dual enhancer-attenuator element ensures transient Cdx2 expression during mouse posterior body formation.Developmental cell · 2025Article
- The exit from naive pluripotency: a platform for the study of enhancer mechanistics.Biochemical Society transactions · 2025Review
- Uncovering hidden enhancers through unbiased in vivo testing.Nature communications · 2025Article
- Single-cell transcriptomics of ventral forebrain progenitors identifies Evf2 enhancer lncRNA-enhancer gene guidance through direct RNA binding and RNP recruitment domains.Nature communications · 2025Article
- Article
- Conservation of regulatory elements with highly diverged sequences across large evolutionary distances.Nature genetics · 2025Article
- Functional characterization of OXTR-associated enhancers.Human molecular genetics · 2025Article
- The mutational landscape and functional effects of noncoding ultraconserved elements in human cancers.Science advances · 2025Article
- Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis.Developmental cell · 2025Article
- A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival.Nature communications · 2024Article
- Article
- Review
- An autoregulatory poison exon in Smndc1 is conserved across kingdoms and influences organism growth.PLoS genetics · 2024Article
- The Evolution of Ultraconserved Elements in Vertebrates.Molecular biology and evolution · 2024Article
- Two redundant transcription factor binding sites in a single enhancer are essential for mammalian sex determination.Nucleic acids research · 2024Article
- DLX genes and proteins in mammalian forebrain development.Development (Cambridge, England) · 2024Review
- Regulatory and evolutionary impact of DNA methylation in two songbird species and their naturally occurring FBMC biology · 2024Article
- The single-cell chromatin landscape in gonadal cell lineage specification.BMC genomics · 2024Article
62 more citing papers are in PubMed but not listed here.
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21 authors.
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Abstract
Non-coding "ultraconserved" regions containing hundreds of consecutive bases of perfect sequence conservation across mammalian genomes can function as distant-acting enhancers. However, initial deletion studies in mice revealed that loss of such extraordinarily constrained sequences had no immediate impact on viability. Here, we show that ultraconserved enhancers are required for normal development. Focusing on some of the longest ultraconserved sites genome wide, located near the essential neuronal transcription factor Arx, we used genome editing to create an expanded series of knockout mice lacking individual or combinations of ultraconserved enhancers. Mice with single or pairwise deletions of ultraconserved enhancers were viable and fertile but in nearly all cases showed neurological or growth abnormalities, including substantial alterations of neuron populations and structural brain defects. Our results demonstrate the functional importance of ultraconserved enhancers and indicate that remarkably strong sequence conservation likely results from fitness deficits that appear subtle in a laboratory setting.
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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.