ArticleGenome biology2024
CpG island turnover events predict evolutionary changes in enhancer activity.
Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Review
- TheInternational journal of hypertension · 2026Article
- Multiple human enhancer RNAs contain long translated open reading frames.Genes & development · 2025Article
- Interrogating the Regulatory Function of HAQERs during Human Cortical Development.bioRxiv : the preprint server for biology · 2025Article
- Roles of transposable elements and DNA methylation in the formation of CpG islands and CpG-depleted regulatory elements.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Author Correction: CpG island turnover events predict evolutionary changes in enhancer activity.Genome biology · 2025Article
- Article
- Reconstructing human-specific regulatory functions in model systems.Current opinion in genetics & development · 2024Review
- Resolving the three-dimensional interactome of Human Accelerated Regions during human and chimpanzee neurodevelopment.bioRxiv : the preprint server for biology · 2024Article
- CpG island turnover events predict evolutionary changes in enhancer activity.Genome biology · 2024Article
Corrections and comments
- Erratum issued
- Update of
Authors and funding
8 authors.
Funding
Abstract
backgroundGenetic changes that modify the function of transcriptional enhancers have been linked to the evolution of biological diversity across species. Multiple studies have focused on the role of nucleotide substitutions, transposition, and insertions and deletions in altering enhancer function. CpG islands (CGIs) have recently been shown to influence enhancer activity, and here we test how their turnover across species contributes to enhancer evolution.
resultsWe integrate maps of CGIs and enhancer activity-associated histone modifications obtained from multiple tissues in nine mammalian species and find that CGI content in enhancers is strongly associated with increased histone modification levels. CGIs show widespread turnover across species and species-specific CGIs are strongly enriched for enhancers exhibiting species-specific activity across all tissues and species. Genes associated with enhancers with species-specific CGIs show concordant biases in their expression, supporting that CGI turnover contributes to gene regulatory innovation. Our results also implicate CGI turnover in the evolution of Human Gain Enhancers (HGEs), which show increased activity in human embryonic development and may have contributed to the evolution of uniquely human traits. Using a humanized mouse model, we show that a highly conserved HGE with a large CGI absent from the mouse ortholog shows increased activity at the human CGI in the humanized mouse diencephalon.
conclusionsCollectively, our results point to CGI turnover as a mechanism driving gene regulatory changes potentially underlying trait evolution in mammals.
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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.