Splitting hares and tortoises: a classification of neuronal immediate early gene transcription based on poised RNA polymerase II

Neuroscience. 2013 Sep 5:247:175-81. doi: 10.1016/j.neuroscience.2013.04.064. Epub 2013 May 24.


Immediate early transcription is an integral part of the neuronal response to environmental stimulation and serves many brain processes including development, learning, triggers of programmed cell death, and reaction to injury and drugs. Following a stimulus, neurons express a select few genes within a short period of time without undergoing de novo protein translation. Referred to as the 'gateway to genetic response', these immediate early genes (IEGs) are either expressed within a few minutes of stimulation or later within the hour. In neuronal IEGs that are expressed rapidly, productive elongation in response to neuronal activity is jump-started by constitutive transcription initiation together with RNA polymerase II stalling in the vicinity of the promoter. IEGs expressed later in the hour do not depend on this mechanism. On the basis of this Polymerase II poising, we propose that the immediate early genes can be grouped in two distinct classes: the rapid and the delayed IEGs. The possible biological relevance of these classes in neurons is discussed.

Keywords: CREB; CREB-regulated transcription coactivator 1; CRTC; GTF; IEG; LTP; MMTV; N-methyl-d-aspartic acid; NELF; NMDA; RNA polymerase II; arc; cAMP response element-binding protein; general transcription factor; immediate early genes; long-term potentiation; mouse mammary tumor viruses; negative elongation factor; neuronal activity; plasticity; transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Genes, Immediate-Early / physiology*
  • Humans
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology
  • Neurons / physiology*
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism*
  • Synapses / genetics
  • Synapses / metabolism
  • Transcription, Genetic / physiology*


  • RNA Polymerase II