Enhancer transcription accurately identifies active enhancers and reveals architectures of transcriptional regulation
Speaker: Robin Andersson, Computational and RNA Biology, Department of Biology
Host: Peter Brodersen (Section for Computational and RNA Biology)
Abstract
Regulatory events at gene-distal enhancers are crucial for the correct control of gene transcription. Despite extensive studies, we still have a very limited understanding of the mechanisms of enhancers and their spatio-temporal activities. In this talk, I will present our recent efforts to characterize enhancer activities based on enhancer transcription.
Systematic categorization of mammalian RNAs by their nuclear stability and by the nature of their transcription initiation allowed us to infer a transcriptional signature of enhancers: enhancers produce bidirectional, exosome-sensitive, relatively short, unspliced RNAs, the generation of which is strongly related to enhancer activity. Based on this signature we produced an atlas of enhancer activities across the majority of human tissues and cell types and across time courses covering a wide range of biological stimuli. The FANTOM5 enhancer atlas allowed us to compare regulatory programs between different cell types and states at unprecedented depth, to identify disease-associated regulatory genetic variants, and to investigate architectures of transcriptional regulation.
Our results indicate that profiling of enhancer RNAs yields high specificity for detecting regulatory activity. They also show apparent similarities between enhancers and promoters, which challenge the established view of enhancers and promoters as distinct entities. Our data further suggest a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation.
Related papers
Robin Andersson et al., An atlas of active enhancers across human cell types and tissues, Nature, 2014.