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.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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Anesthetics, Local / pharmacology
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Animals
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism*
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Cells, Cultured
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Cerebral Cortex / cytology
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Chromatin Immunoprecipitation / methods
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Embryo, Mammalian
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Excitatory Amino Acid Antagonists / pharmacology
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Exons / drug effects
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Exons / physiology
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Gene Expression Profiling / methods
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Immediate-Early Proteins / genetics
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Immediate-Early Proteins / metabolism*
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Neurons / drug effects
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Neurons / metabolism*
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Oligonucleotide Array Sequence Analysis / methods
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Phosphopyruvate Hydratase / metabolism
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RNA Interference / physiology
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RNA Polymerase II / genetics
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RNA Polymerase II / metabolism*
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RNA, Messenger / metabolism
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RNA, Small Interfering / pharmacology
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Rats
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Rats, Sprague-Dawley
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Serine / metabolism
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Tetrodotoxin / pharmacology
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Time Factors
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Transcription Factors / metabolism
Substances
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Anesthetics, Local
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Apoptosis Regulatory Proteins
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Excitatory Amino Acid Antagonists
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Immediate-Early Proteins
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Muscle Proteins
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Nol3 protein, rat
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RNA, Messenger
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RNA, Small Interfering
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Transcription Factors
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negative elongation factor
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Tetrodotoxin
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Serine
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2-Amino-5-phosphonovalerate
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RNA Polymerase II
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Phosphopyruvate Hydratase
Associated data
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GEO/GSE22622
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GEO/GSE22878