ArticleMolecular biology and evolution2010
The importance of being cis: evolution of orthologous fish and mammalian enhancer activity.
Article in Molecular biology and evolution, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Evolutionary transfer learning enables organism-wide inference of mammalian enhancer landscapes.bioRxiv : the preprint server for biology · 2026Article
- Cis-regulatory control of mammalian Trps1 gene expression.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2024Article
- Article
- Enhancer Function and Evolutionary Roles of Human Accelerated Regions.Annual review of genetics · 2022Review
- Functional in vivo characterization of sox10 enhancers in neural crest and melanoma development.Communications biology · 2021Article
- A Non-coding HES1 Variant Predisposes Children to Congenital Heart Disease in Chinese Population.Frontiers in cell and developmental biology · 2021Article
- Learning and interpreting the gene regulatory grammar in a deep learning framework.PLoS computational biology · 2020Article
- Understanding the genetics of neuropsychiatric disorders: the potential role of genomic regulatory blocks.Molecular psychiatry · 2020Review
- A novel measure of non-coding genome conservation identifies genomic regulatory blocks within primates.Bioinformatics (Oxford, England) · 2019Article
- Article
- Prediction of gene regulatory enhancers across species reveals evolutionarily conserved sequence properties.PLoS computational biology · 2018Article
- Gene Regulatory Enhancers with Evolutionarily Conserved Activity Are More Pleiotropic than Those with Species-Specific Activity.Genome biology and evolution · 2017Article
- Topologically associating domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation.Nature communications · 2017Article
- Phenoscape: Identifying Candidate Genes for Evolutionary Phenotypes.Molecular biology and evolution · 2016Article
- Functional Diversification of Motor Neuron-specific Isl1 Enhancers during Evolution.PLoS genetics · 2015Article
- Article
- Pervasive divergence of transcriptional gene regulation in Caenorhabditis nematodes.PLoS genetics · 2014Article
- Conserved noncoding elements follow power-law-like distributions in several genomes as a result of genome dynamics.PloS one · 2014Article
- A reporter assay in lamprey embryos reveals both functional conservation and elaboration of vertebrate enhancers.PloS one · 2014Article
- The mystery of extreme non-coding conservation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2013Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Conserved noncoding elements (CNEs) in vertebrate genomes often act as developmental enhancers, but a critical issue is how well orthologous CNE sequences retain the same activity in their respective species, a characteristic important for generalization of model organism studies. To quantify how well CNE enhancer activity has been preserved, we compared the anatomy-specific activities of 41 zebra fish CNEs in zebra fish embryos with the activities of orthologous human CNEs in mouse embryos. We found that 13/41 (∼30%) of the orthologous CNE pairs exhibit conserved positive activity in zebra fish and mouse. Conserved positive activity is only weakly associated with either sequence conservation or the absence of bases undergoing accelerated evolution. A stronger effect is that disparate activity is associated with transcription factor binding site divergence. To distinguish the contributions of cis- versus trans-regulatory changes, we analyzed 13 CNEs in a three-way experimental comparison: human CNE tested in zebra fish, human CNE tested in mouse, and orthologous zebra fish CNE tested in zebra fish. Both cis- and trans-changes affect a significant fraction of CNEs, although human and zebra fish sequences exhibit disparate activity in zebra fish (indicating cis regulatory changes) twice as often as human sequences show disparate activity when tested in mouse and zebra fish (indicating trans regulatory changes). In all four cases where the zebra fish and human CNE display a similar expression pattern in zebra fish, the human CNE also displays a similar expression pattern in mouse. This suggests that the endogenous enhancer activity of ∼30% of human CNEs can be determined from experiments in zebra fish alone, and to identify these CNEs, both the zebra fish and the human sequences should be tested.
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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.