ArticleGenome research2011
Genome-wide identification of conserved regulatory function in diverged sequences.
Article in Genome research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Motif-based models accurately predict cell type-specific distal regulatory elements.Nature communications · 2025Article
- Conservation of regulatory elements with highly diverged sequences across large evolutionary distances.Nature genetics · 2025Article
- Decoding polygenic diseases: advances in noncoding variant prioritization and validation.Trends in cell biology · 2024Review
- Review
- Decoding enhancer complexity with machine learning and high-throughput discovery.Genome biology · 2023Review
- Identification of enhancers responsible for the coordinated expression of myosin heavy chain isoforms in skeletal muscle.BMC genomics · 2022Article
- Review
- Identification of limb-specific Lmx1b auto-regulatory modules with Nail-patella syndrome pathogenicity.Nature communications · 2021Article
- Learning a genome-wide score of human-mouse conservation at the functional genomics level.Nature communications · 2021Article
- SeqEnhDL: sequence-based classification of cell type-specific enhancers using deep learning models.BMC research notes · 2021Article
- Enhancer grammar in development, evolution, and disease: dependencies and interplay.Developmental cell · 2021Review
- Article
- MPRAdecoder: Processing of the Raw MPRA Data WithFrontiers in genetics · 2021Article
- Functional Conservation of Divergent p63-BoundFrontiers in genetics · 2020Article
- Article
- Using zebrafish to study skeletal genomics.Bone · 2019Review
- Prediction of gene regulatory enhancers across species reveals evolutionarily conserved sequence properties.PLoS computational biology · 2018Article
- A screen for deeply conserved non-coding GWAS SNPs uncovers a MIR-9-2 functional mutation associated to retinal vasculature defects in human.Nucleic acids research · 2018Article
- Multiple enhancer regions govern the transcription of CCN2 during embryonic development.Journal of cell communication and signaling · 2018Article
- Identifying Novel Enhancer Elements with CRISPR-Based Screens.ACS chemical biology · 2018Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Plasticity of gene regulatory encryption can permit DNA sequence divergence without loss of function. Functional information is preserved through conservation of the composition of transcription factor binding sites (TFBS) in a regulatory element. We have developed a method that can accurately identify pairs of functional noncoding orthologs at evolutionarily diverged loci by searching for conserved TFBS arrangements. With an estimated 5% false-positive rate (FPR) in approximately 3000 human and zebrafish syntenic loci, we detected approximately 300 pairs of diverged elements that are likely to share common ancestry and have similar regulatory activity. By analyzing a pool of experimentally validated human enhancers, we demonstrated that 7/8 (88%) of their predicted functional orthologs retained in vivo regulatory control. Moreover, in 5/7 (71%) of assayed enhancer pairs, we observed concordant expression patterns. We argue that TFBS composition is often necessary to retain and sufficient to predict regulatory function in the absence of overt sequence conservation, revealing an entire class of functionally conserved, evolutionarily diverged regulatory elements that we term "covert."
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