title: Rapid activity-induced transcription of Arc and other IEGs relies on poised RNA polymerase II.
abstract: 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.
authors.affiliation: Laboratory of Neurobiology, National Institute of Environmental Health Sciences, US National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Ramendra N
authors.initials: RN
authors.lastname: Saha
authors.forename: Erin M
authors.initials: EM
authors.lastname: Wissink
authors.forename: Emma R
authors.initials: ER
authors.lastname: Bailey
authors.forename: Meilan
authors.initials: M
authors.lastname: Zhao
authors.forename: David C
authors.initials: DC
authors.lastname: Fargo
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Hwang
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Daigle
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Fenn
authors.forename: Karen
authors.initials: K
authors.lastname: Adelman
authors.forename: Serena M
authors.initials: SM
authors.lastname: Dudek
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D047369:Chromatin Immunoprecipitation / Q000379:methods; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005091:Exons / Q000187:drug effects / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D051017:Apoptosis Regulatory Proteins; D018691:Excitatory Amino Acid Antagonists; D017874:Immediate-Early Proteins; D009124:Muscle Proteins; C491788:Nol3 protein, rat; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; C118437:negative elongation factor; D013779:Tetrodotoxin; D012694:Serine; D015763:2-Amino-5-phosphonovalerate; D012319:RNA Polymerase II; D010751:Phosphopyruvate Hydratase