Integrator regulates transcriptional initiation and pause release following activation

Mol Cell. 2014 Oct 2;56(1):128-139. doi: 10.1016/j.molcel.2014.08.004. Epub 2014 Sep 4.

Abstract

In unicellular organisms, initiation is the rate-limiting step in transcription; in metazoan organisms, the transition from initiation to productive elongation is also important. Here, we show that the RNA polymerase II (RNAPII)-associated multiprotein complex, Integrator, plays a critical role in both initiation and the release of paused RNAPII at immediate early genes (IEGs) following transcriptional activation by epidermal growth factor (EGF) in human cells. Integrator is recruited to the IEGs in a signal-dependent manner and is required to engage and recruit the super elongation complex (SEC) to EGF-responsive genes to allow release of paused RNAPII and productive transcription elongation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epidermal Growth Factor / metabolism
  • Epidermal Growth Factor / physiology
  • HeLa Cells
  • Humans
  • RNA Polymerase II / metabolism*
  • Transcription Initiation, Genetic*
  • Transcriptional Activation*

Substances

  • Epidermal Growth Factor
  • RNA Polymerase II

Associated data

  • GEO/GSE58255