ArticleGenome research2005
A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts.
Article in Genome research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed.
- The insertion of an ATTTC repeat in an Alu element hyperactivates a neurodevelopmental enhancer in spinocerebellar ataxia type 37.Cell reports · 2026Article
- Conserved Noncoding Elements Evolve Around the Same Genes Throughout Metazoan Evolution.Genome biology and evolution · 2024Article
- GC-biased gene conversion drives accelerated evolution of ultraconserved elements in mammalian and avian genomes.Genome research · 2023Article
- Evolutionary constraint and innovation across hundreds of placental mammals.Science (New York, N.Y.) · 2023Article
- Multi-omics approach dissects cis-regulatory mechanisms underlying North Carolina macular dystrophy, a retinal enhanceropathy.American journal of human genetics · 2022Article
- Comparative 3D genome architecture in vertebrates.BMC biology · 2022Article
- The importance of considering regulatory domains in genome-wide analyses - the nearest gene is often wrong!Biology open · 2022Review
- Multidimensional chromatin profiling of zebrafish pancreas to uncover and investigate disease-relevant enhancers.Nature communications · 2022Article
- Perfect and imperfect views of ultraconserved sequences.Nature reviews. Genetics · 2022Review
- Differential enrichment of H3K9me3 at annotated satellite DNA repeats in human cell lines and during fetal development in mouse.Epigenetics & chromatin · 2021Article
- Functional and structural basis of extreme conservation in vertebrate 5' untranslated regions.Nature genetics · 2021Article
- Heart Enhancers: Development and Disease Control at a Distance.Frontiers in genetics · 2021Review
- Impact of Genetic Variation in Gene Regulatory Sequences: A Population Genomics Perspective.Frontiers in genetics · 2021Review
- Iroquois Homeobox Protein 2 Identified as a Potential Biomarker for Parkinson's Disease.International journal of molecular sciences · 2020Article
- CNEr: A toolkit for exploring extreme noncoding conservation.PLoS computational biology · 2019Article
- Article
- Functional Conservation of a Developmental Switch in Mammals since the Jurassic Age.Molecular biology and evolution · 2019Article
- Article
- Iroquois Homeodomain transcription factors in ventricular conduction system and arrhythmia.International journal of medical sciences · 2018Review
- Conserved non-coding elements: developmental gene regulation meets genome organization.Nucleic acids research · 2017Review
37 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies of the genome architecture of vertebrates have uncovered two unforeseen aspects of its organization. First, large regions of the genome, called gene deserts, are devoid of protein-coding sequences and have no obvious biological role. Second, comparative genomics has highlighted the existence of an array of highly conserved non-coding regions (HCNRs) in all vertebrates. Most surprisingly, these structural features are strongly associated with genes that have essential functions during development. Among these, the vertebrate Iroquois (Irx) genes stand out on both fronts. Mammalian Irx genes are organized in two clusters (IrxA and IrxB) that span >1 Mb each with no other genes interspersed. Additionally, a large number of HCNRs exist within Irx clusters. We have systematically examined the enhancer activity of HCNRs from the IrxB cluster using transgenic Xenopus and zebrafish embryos. Most of these HCNRs are active in subdomains of endogenous Irx expression, and some are candidates to contain shared enhancers of neighboring genes, which could explain the evolutionary conservation of Irx clusters. Furthermore, HCNRs present in tetrapod IrxB but not in fish may be responsible for novel Irx expression domains that appeared after their divergence. Finally, we have performed a more detailed analysis on two IrxB ultraconserved non-coding regions (UCRs) duplicated in IrxA clusters in similar relative positions. These four regions share a core region highly conserved among all of them and drive expression in similar domains. However, inter-species conserved sequences surrounding the core, specific for each of these UCRs, are able to modulate their expression.
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