NDLI: Comparative genomics analyses reveal sequence determinants underlying interspecies variations in injury-responsive enhancers

Content Provider	Springer Nature : BioMed Central
Author	Ji, Luzhang Shi, Yuanyuan Bian, Qian
Abstract	Background Injury 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. Results We 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. Conclusions By 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.
Related Links	https://bmcgenomics.biomedcentral.com/counter/pdf/10.1186/s12864-023-09283-8.pdf
Ending Page	21
Page Count	21
Starting Page	1
File Format	HTM / HTML
ISSN	14712164
DOI	10.1186/s12864-023-09283-8
Journal	BMC Genomics
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2023-04-05
Access Restriction	Open
Subject Keyword	Life Sciences Microarrays Proteomics Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics Injury-responsive enhancer Transcriptional response AP-1 ETS Motif frequency
Content Type	Text
Resource Type	Article
Subject	Biotechnology Genetics
Journal Impact Factor	3.5/2023
5-Year Journal Impact Factor	4.1/2023

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