RT Journal
A1 Kim, Yoon Jung
A1 Xie, Peng
A1 Cao, Lian
A1 Zhang, Michael Q.
A1 Kim, Tae Hoon
T1 Global transcriptional activity dynamics reveal functional enhancer RNAs
JF Genome Research 
JO Genome Research 
YR 2018 
FD December 01 
VO 28 
IS 12 
SP 1799 
OP 1811 
DO 10.1101/gr.233486.117 
UL http://genome.cshlp.org/content/28/12/1799.abstract 
AB Active enhancers of the human genome generate long noncoding transcripts known as enhancer RNAs (eRNAs). How dynamic transcriptional changes of eRNAs are physically and functionally linked with target gene transcription remains unclear. To investigate the dynamic functional relationships among eRNAs and target promoters, we obtained a dense time series of GRO-seq and ChIP-seq data to generate a time-resolved enhancer activity map of a cell undergoing an innate antiviral immune response. Dynamic changes in eRNA and pre-mRNA transcription activities suggest distinct regulatory roles of enhancers. Using a criterion based on proximity and transcriptional inducibility, we identified 123 highly confident pairs of virus-inducible enhancers and their target genes. These enhancers interact with their target promoters transiently and concurrently at the peak of gene activation. Accordingly, their physical disassociation from the promoters is likely involved in post-induction repression. Functional assessments further establish that these eRNAs are necessary for full induction of the target genes and that a complement of inducible eRNAs functions together to achieve full activation. Lastly, we demonstrate the potential for eRNA-targeted transcriptional reprogramming through targeted reduction of eRNAs for a clinically relevant gene, TNFSF10, resulting in a selective control of interferon-induced apoptosis.