# Epromoters bind key stress-related transcription factors to regulate clusters of stress response genes

## TL;DR

This study shows that Epromoters, which act as both promoters and enhancers, regulate clusters of stress-response genes by recruiting key transcription factors during stress.

## Contribution

The paper introduces Epromoters as central regulatory elements that coordinate gene clusters during stress responses.

## Key findings

- Co-induced stress-response genes are often located in close genomic proximity.
- Epromoters regulate gene clusters independently of their genomic location.
- Epromoter-regulated clusters are found across various stress and inflammatory models.

## Abstract

Cellular and environmental stress triggers the rapid and global reprogramming of gene transcription by coordinated recruitment of a limited number of key inducible transcription factors to cis-regulatory elements. Here, we performed a comprehensive analysis of different stress models and observed that co-induced genes are generally located in close genomic proximity. By integrating gene expression and transcription factor binding resources across different stress models, we identify an enrichment for clusters in which only one of the clusters’ promoters recruits the key transcription factors, reminiscent of Epromoters—a type of cis-regulatory element that displays both promoter and enhancer function. Epromoter-regulated clusters were frequently found regardless of the stress or inflammatory response. Predicted Epromoters displayed enhancer activity and regulated clusters of stress-response genes independently of their genomic location. These findings imply that Epromoters are central regulatory elements that control gene clusters in response to acute perturbations.

Stress responses rewire transcription through specialized regulatory elements. This study reveals that Epromoters—dual elements with promoter-enhancer functions—orchestrate coordinated transcriptional responses of clustered genes to diverse stress signals.

Co-induced stress-response genes are often located in close genomic proximity.Only one promoter per cluster typically recruits key stress-activated transcription factors.These “hub” promoters show enhancer-like activity, consistent with Epromoter function.Epromoter-regulated clusters occur across different stress and inflammatory models.Epromoters enable coordinated regulation of gene clusters independently of genomic context.

Co-induced stress-response genes are often located in close genomic proximity.

Only one promoter per cluster typically recruits key stress-activated transcription factors.

These “hub” promoters show enhancer-like activity, consistent with Epromoter function.

Epromoter-regulated clusters occur across different stress and inflammatory models.

Epromoters enable coordinated regulation of gene clusters independently of genomic context.

Epromoters bind key stress-related transcription factors to regulate clusters of stress response genes.