The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription

Abstract

Gene expression is regulated by promoters, which initiate transcription, and enhancers, which control their temporal and spatial activity. However, the discovery that mammalian enhancers also initiate transcription questions the inherent differences between enhancers and promoters. Here, we investigate the transcriptional properties of enhancers during Drosophila embryogenesis using characterized developmental enhancers. We show that while the timing of enhancer transcription is generally correlated with enhancer activity, the levels and directionality of transcription are highly varied among active enhancers. To assess how this impacts function, we developed a dual transgenic assay to simultaneously measure enhancer and promoter activities from a single element in the same embryo. Extensive transgenic analysis revealed a relationship between the direction of endogenous transcription and the ability to function as an enhancer or promoter in vivo, although enhancer RNA (eRNA) production and activity are not always strictly coupled. Some enhancers (mainly bidirectional) can act as weak promoters, producing overlapping spatio-temporal expression. Conversely, bidirectional promoters often act as strong enhancers, while unidirectional promoters generally cannot. The balance between enhancer and promoter activity is generally reflected in the levels and directionality of eRNA transcription and is likely an inherent sequence property of the elements themselves.

Molecular mechanisms driving transcriptional stress responses

“…With the advent of high-throughput sequencing, enhancers have been shown to produce short and unstable transcripts termed enhancer RNAs (eRNAs) 82–83 , and to share many structural features with promoters 35,84–85 . Especially in mammals 35 , but also in flies 36 , eRNAs are in general produced from divergent regulatory elements, which harbour two core initiation regions [G] that launch transcription in opposing directions.…”

“…Concurrent with the transcriptional reprogramming of genes, heat stress or celastrol treatment cause an overall increase in Pol II density at enhancers 11,28 . Since enhancer transcription, in general, correlates with its enhancing capacity 84–85 , the increased transcription at many enhancers likely indicates their increased activity 11,28 . However, the collectively higher transcription at enhancers upon heat or celastrol treatment may reflect the increased availability of Pol II in the cell (discussed above), contributing to the rapid changes in enhancer transcription (FIG.…”

Developmental Transcriptional Enhancers: A Subtle Interplay between Accessibility and Activity

“…[ 87 ] However, recent studies contest this model by demonstrating that eRNA transcription occurs also at inactive enhancers with repressive histone marks [ 88 ] or by identifying active enhancers with undetectable eRNA transcription. [ 89 ] Interestingly, the rate of transcription initiation at the target promoter has been shown to correlate more strongly with the overall enhancer accessibility than the amount of transcribed eRNA. [ 88 ]…”

Persistent chromatin states, pervasive transcription, and sharedcis-regulatory sequences have shaped theC. elegansgenome

“…Rather gene activity may be fundamentally regulated by directional cis-acting elements (i.e. promoters) (Henriques et al 2018;Mikhaylichenko et al 2018) and posttranscriptional mechanisms that control mRNA abundance.…”