Journal Article

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

Daigle, Kelly R, Adelman, Karen, Bailey, Emma R, Dudek, Serena M, Saha, Ramendra N, Zhao, Meilan, Fenn, J Daniel, Hwang, Ji-Yeon, Fargo, David C, Wissink, Erin M

2011

Overview

Immediate early genes are rapidly transcribed in response to neuronal activity, but the underlying mechanism is unclear. The authors show that this rapid transcription is mediated by a stalled RNA polymerase II, poised just downstream of the transcription start site. RNAi-depletion of negative elongation factor compromises the rapid transcription. 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, reduced the Pol II occupancy of the Arc promoter and compromised the rapid induction of Arc and other IEGs. In contrast, reduction of Pol II stalling did not prevent transcription of IEGs that were expressed later and largely lacked promoter-proximal Pol II stalling. Together, our data strongly indicate that the rapid induction of neuronal IEGs requires poised Pol II and suggest a role for this mechanism in a wide variety of transcription-dependent processes, including learning and memory.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 2-Amino-5-phosphonovalerate - pharmacology / 631/337/572 / 631/378 / 631/378/340 / Anesthetics, Local - pharmacology / Animal Genetics and Genomics / Animals / Antibodies / Apoptosis Regulatory Proteins - genetics / Apoptosis Regulatory Proteins - metabolism / Behavioral Sciences / Biological Techniques / Biomedical and Life Sciences / Biomedicine / Cells, Cultured / Cerebral Cortex - cytology / Chromatin Immunoprecipitation - methods / Embryo, Mammalian / Environmental health / Excitatory Amino Acid Antagonists - pharmacology / Exons - drug effects / Exons - physiology / Gene Expression Profiling - methods / Gene Expression Regulation - drug effects / Gene Expression Regulation - physiology / Genes / Genetic aspects / Genetic transcription / Health sciences / Immediate-Early Proteins - genetics / Immediate-Early Proteins - metabolism / Muscle Proteins - genetics / Muscle Proteins - metabolism / Neurobiology / Neurons / Neurons - drug effects / Neurons - metabolism / Neurosciences / Oligonucleotide Array Sequence Analysis - methods / Phosphopyruvate Hydratase - metabolism / Physiological aspects / Rats / Rats, Sprague-Dawley / RNA Interference - physiology / RNA polymerase / RNA Polymerase II - genetics / RNA Polymerase II - metabolism / RNA polymerases / RNA, Messenger - metabolism / RNA, Small Interfering - pharmacology / Serine - metabolism / Tetrodotoxin - pharmacology / Time Factors / Transcription Factors - metabolism