Integrator mediates the biogenesis of enhancer RNAs
#MMPMID26308897
Lai F
; Gardini A
; Zhang A
; Shiekhattar R
Nature
2015[Sep]; 525
(7569
): 399-403
PMID26308897
show ga
Integrator is a multi-subunit complex stably associated with the carboxy-terminal
domain (CTD) of RNA polymerase II (RNAPII). Integrator is endowed with a core
catalytic RNA endonuclease activity, which is required for the 3'-end processing
of non-polyadenylated, RNAPII-dependent, uridylate-rich, small nuclear RNA genes.
Here we examine the requirement of Integrator in the biogenesis of transcripts
derived from distal regulatory elements (enhancers) involved in tissue- and
temporal-specific regulation of gene expression in metazoans. Integrator is
recruited to enhancers and super-enhancers in a stimulus-dependent manner.
Functional depletion of Integrator subunits diminishes the signal-dependent
induction of enhancer RNAs (eRNAs) and abrogates stimulus-induced
enhancer-promoter chromatin looping. Global nuclear run-on and RNAPII profiling
reveals a role for Integrator in 3'-end cleavage of eRNA primary transcripts
leading to transcriptional termination. In the absence of Integrator, eRNAs
remain bound to RNAPII and their primary transcripts accumulate. Notably, the
induction of eRNAs and gene expression responsiveness requires the catalytic
activity of Integrator complex. We propose a role for Integrator in biogenesis of
eRNAs and enhancer function in metazoans.
free
free
free
