TY - JOUR T1 - Skill Learning Modulates RNA Pol II Poising at Immediate Early Genes in the Adult Striatum JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0074-17.2017 SP - ENEURO.0074-17.2017 AU - Pedro Galvão-Ferreira AU - Michal Lipinski AU - Fernando Santos AU - Angel Barco AU - Rui M. Costa Y1 - 2017/04/06 UR - http://www.eneuro.org/content/early/2017/04/06/ENEURO.0074-17.2017.abstract N2 - A multi-layered complexity of epigenetic and transcriptional regulatory mechanisms underlies neuronal activity-dependent gene transcription. The regulation of RNA Pol II progression along the transcription cycle, from promoter-proximal poising (with RNA Pol II paused at promoter-proximal regions, characterized by a Ser5P+-rich and Ser2P+-poor RPB1 C-terminal domain) to active elongation, has emerged as a major step in transcriptional regulation across several organisms, tissues and developmental stages, including the nervous system. However, it is not known whether this mechanism is modulated by experience. We investigated the impact of learning a motor skill on RNA Pol II phosphorylation dynamics in the adult mouse striatum. We uncovered that learning modulates the in vivo striatal phosphorylation dynamics of the C-terminal domain of the RNA Pol II RPB1 subunit, leading to an increased poising index in trained mice. We found that this modulation occurs at immediate early genes (IEGs), with increased poising of RNA Pol II at both Arc and Fos genes, but not at constitutively expressed genes. Furthermore, we confirmed that this was learning-dependent, and not just regulated by context or motor activity. These experiments demonstrate a novel phenomenon of learning induced transcriptional modulation in adult brain, which may have implications for our understanding of learning, memory allocation, and consolidation.Significance Statement RNA Pol II poising is a powerful way of modulating gene transcription. Although previous studies have shown activity-dependent changes in RNA Pol II poising in vitro, the modulation of RNA Pol II poising by experience has not been investigated. In this study, we show that learning modulates striatal phosphorylation dynamics of the RNA Pol II RPB1 subunit in vivo, leading to an increased poising index in trained mice. We also show that learning modulates RPB1 phosphorylation at immediate early genes, with increased poising of RNA Pol II in both Arc and Fos genes. Our experiments demonstrate a new phenomenon of learning-induced transcriptional modulation in the adult brain that may be involved in neural circuit-priming, memory consolidation and recall. ER -