Global transcriptional activity dynamics reveal functional enhancer RNAs

Area of Science:

• Genomics
• Molecular Biology
• Immunology

Background:

• Active enhancers in the human genome produce enhancer RNAs (eRNAs).
• The precise physical and functional link between dynamic eRNA transcription and target gene transcription is not fully understood.

Purpose of the Study:

• To investigate the dynamic functional relationships between eRNAs and their target promoters.
• To elucidate the role of eRNAs in the innate antiviral immune response.

Main Methods:

• Utilized dense time-series GRO-seq and ChIP-seq data to create a time-resolved enhancer activity map.
• Identified virus-inducible enhancer-target gene pairs based on proximity and transcriptional inducibility.
• Performed functional assessments and targeted eRNA reduction experiments.

Main Results:

• Identified 123 virus-inducible enhancer-target gene pairs.
• Demonstrated transient and concurrent interaction between enhancers and target promoters during peak gene activation.
• Established that eRNAs are necessary for full target gene induction and function collectively.
• Showcased eRNA-targeted transcriptional reprogramming for the gene TNFSF10, controlling interferon-induced apoptosis.

Conclusions:

• Dynamic eRNA transcription plays distinct regulatory roles in enhancer function.
• eRNAs are crucial for the robust activation of target genes during immune responses.
• Targeting eRNAs offers a potential strategy for transcriptional reprogramming and therapeutic intervention.