Transcriptomics

Dataset Information

62

Neurotoxin tetrodotoxin TTX withdrawal induced neuronal activity: RNA Pol II is poised for rapid induction of arc and other neuronal VF-IEGs


ABSTRACT: Transcription of immediate early genes (IEGs) in neurons is exquisitely sensitive to neuronal activity, but the mechanism underlying the earliest of these transcription events is largely unknown. Here we demonstrate that very fast IEGs (VF-IEGs) such as arc/arg3.1 are poised for rapid transcription by the stalling of RNA Polymerase II (Pol II) just downstream of the transcription start site. RNAi-depletion of two subunits of a mediator of Pol II stalling, Negative Elongation Factor, reduces Pol II occupancy of the arc promoter and compromises rapid induction of arc and other VF-IEGs. In contrast, reduction of Pol II stalling did not prevent expression of other fast IEGs (F-IEGs). These F-IEGs are expressed with comparatively slower kinetics and largely lack promoter proximal Pol II stalling. Taken together, our data strongly indicate that very fast kinetics of neuronal IEG expression require poised Pol II and suggest a role for this mechanism in transcription-dependent learning and memory. TTX withdrawal induced neuronal activity. To study activity-induced gene expression, neurons were treated with TTX for 48 hours and then TTX was washed out either for 15 minutes (W15) or for 45 minutes (W45). Gene expression was measured in these two groups in comparison to TTX treated neurons.

ORGANISM(S): Rattus norvegicus  

SUBMITTER: Ramendra N Saha   NIEHS Microarray Core  Emma R Bailey 

PROVIDER: E-GEOD-22622 | ArrayExpress | 2011-04-14

SECONDARY ACCESSION(S): GSE22622PRJNA128517

REPOSITORIES: GEO, ArrayExpress

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Publications

Rapid activity-induced transcription of Arc and other IEGs relies on poised RNA polymerase II.

Saha Ramendra N RN   Wissink Erin M EM   Bailey Emma R ER   Zhao Meilan M   Fargo David C DC   Hwang Ji-Yeon JY   Daigle Kelly R KR   Fenn J Daniel JD   Adelman Karen K   Dudek Serena M SM  

Nature neuroscience 20110529 7


Transcription of immediate early genes (IEGs) in neurons is highly sensitive to neuronal activity, but the mechanism underlying these early transcription events is largely unknown. We found that several IEGs, such as Arc (also known as Arg3.1), are poised for near-instantaneous transcription by the stalling of RNA polymerase II (Pol II) just downstream of the transcription start site in rat neurons. Depletion through RNA interference of negative elongation factor, a mediator of Pol II stalling,  ...[more]

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