Neuroscience Forefront ReviewSplitting Hares and Tortoises: A classification of neuronal immediate early gene transcription based on poised RNA polymerase II

•Immediate early genes (IEGs) can be induced with either rapid or delayed responses.•RNA Pol II is poised in proximity of the promoters of arc and other rapid IEGs.•Rapid induction of arc and other rapid IEGs is dependent on poised Pol II.•Delayed IEGs lack poised Pol II in most cases and are NELF knockdown insensitive.

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.