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2018 ; 32
(1
): 26-41
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Widespread transcriptional pausing and elongation control at enhancers
#MMPMID29378787
Henriques T
; Scruggs BS
; Inouye MO
; Muse GW
; Williams LH
; Burkholder AB
; Lavender CA
; Fargo DC
; Adelman K
Genes Dev
2018[Jan]; 32
(1
): 26-41
PMID29378787
show ga
Regulation by gene-distal enhancers is critical for cell type-specific and
condition-specific patterns of gene expression. Thus, to understand the basis of
gene activity in a given cell type or tissue, we must identify the precise
locations of enhancers and functionally characterize their behaviors. Here, we
demonstrate that transcription is a nearly universal feature of enhancers in
Drosophila and mammalian cells and that nascent RNA sequencing strategies are
optimal for identification of both enhancers and superenhancers. We dissect the
mechanisms governing enhancer transcription and discover remarkable similarities
to transcription at protein-coding genes. We show that RNA polymerase II (RNAPII)
undergoes regulated pausing and release at enhancers. However, as compared with
mRNA genes, RNAPII at enhancers is less stable and more prone to early
termination. Furthermore, we found that the level of histone H3 Lys4 (H3K4)
methylation at enhancers corresponds to transcriptional activity such that highly
active enhancers display H3K4 trimethylation rather than the H3K4 monomethylation
considered a hallmark of enhancers. Finally, our work provides insights into the
unique characteristics of superenhancers, which stimulate high-level gene
expression through rapid pause release; interestingly, this property renders
associated genes resistant to the loss of factors that stabilize paused RNAPII.
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