ArticleBMC genomics2023
Comparative genomics analyses reveal sequence determinants underlying interspecies variations in injury-responsive enhancers.
Article in BMC genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 2 citations in OpenAlex.
- Common and specific gene regulatory programs in zebrafish caudal fin regeneration at single-cell resolution.Genome research · 2025Article
- A screen for regeneration-associated silencer regulatory elements in zebrafish.Developmental cell · 2024Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundInjury induces profound transcriptional remodeling events, which could lead to only wound healing, partial tissue repair, or perfect regeneration in different species. Injury-responsive enhancers (IREs) are cis-regulatory elements activated in response to injury signals, and have been demonstrated to promote tissue regeneration in some organisms such as zebrafish and flies. However, the functional significances of IREs in mammals remain elusive. Moreover, whether the transcriptional responses elicited by IREs upon injury are conserved or specialized in different species, and what sequence features may underlie the functional variations of IREs have not been elucidated.
resultsWe identified a set of IREs that are activated in both regenerative and non-regenerative neonatal mouse hearts upon myocardial ischemia-induced damage by integrative epigenomic and transcriptomic analyses. Motif enrichment analysis showed that AP-1 and ETS transcription factor binding motifs are significantly enriched in both zebrafish and mouse IREs. However, the IRE-associated genes vary considerably between the two species. We further found that the IRE-related sequences in zebrafish and mice diverge greatly, with the loss of IRE inducibility accompanied by a reduction in AP-1 and ETS motif frequencies. The functional turnover of IREs between zebrafish and mice is correlated with changes in transcriptional responses of the IRE-associated genes upon injury. Using mouse cardiomyocytes as a model, we demonstrated that the reduction in AP-1 or ETS motif frequency attenuates the activation of IREs in response to hypoxia-induced damage.
conclusionsBy performing comparative genomics analyses on IREs, we demonstrated that inter-species variations in AP-1 and ETS motifs may play an important role in defining the functions of enhancers during injury response. Our findings provide important insights for understanding the molecular mechanisms of transcriptional remodeling in response to injury across species.
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