2023 Articles
Reporter gene assays and chromatin-level assays define substantially non-overlapping sets of enhancer sequences
Background
Transcriptional enhancers are essential for gene regulation, but how these regulatory elements are best defined remains a significant unresolved question. Traditional definitions rely on activity-based criteria such as reporter gene assays, while more recently, biochemical assays based on chromatin-level phenomena such as chromatin accessibility, histone modifications, and localized RNA transcription have gained prominence.
Results
We examine here whether these two types of definitions, activity-based and chromatin-based, effectively identify the same sets of sequences. We find that, concerningly, the overlap between the two groups is strikingly limited. Few of the data sets we compared displayed statistically significant overlap, and even for those, the degree of overlap was typically small (below 40% of sequences). Moreover, a substantial batch effect was observed in which experiment set rather than experimental method was a primary driver of whether or not chromatin-defined enhancers showed a strong overlap with reporter gene-defined enhancers.
Conclusions
Our results raise important questions as to the appropriateness of both old and new enhancer definitions, and suggest that new approaches are required to reconcile the poor agreement among existing methods for defining enhancers.
Files
- 12864_2023_Article_9123.pdf application/pdf 953 KB Download File
Also Published In
- Title
- BMC Genomics
- DOI
- https://doi.org/10.1186/s12864-023-09123-9
More About This Work
- Published Here
- July 22, 2024
Related Items
Notes
Cis-regulation, Enhancer, CRM, Gene regulation, Reporter gene, ATAC-seq, Histone modification